By that point, the president had already received Price’s resignation letter. In a statement shortly afterward, the White House said Trump would designate Don J. Wright as acting secretary. Wright has been the acting assistant secretary for health and director of the Office of Disease Prevention and Health Promotion.

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Price submitted a four-paragraph resignation letter in which he said he regretted “that the recent events have created a distraction” from the administration’s objectives. “Success on these issues is more important than any one person,” he continued.

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Not long after, HHS staff received a message from Price praising employees as “dedicated, committed” and saying it had been “a great joy” to serve with them.

He closed: “Duty is Ours — Results are the Lord’s!”

Price had given every indication this week that he intended to fight to keep his job. During an interview Thursday night on Fox News, he said he planned “to not only regain the trust of the American people, but gain the trust of the administration and the president.”

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And in an email on Friday with a time stamp of 4:43 p.m. — just minutes before the White House announced his departure — Price detailed personnel changes and a “strategic shift” initiative that gave no hint of his own move.

Trump’s advisers said the president was particularly discomfited by Price’s behavior because he’d run as a champion for “forgotten” Americans for whom costly charter-plane travel seemed particularly egregious.

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“It speaks to people who think Washington is already beyond hope and out of touch,” said Barry Bennett, a campaign adviser last year.

The similar accusations swirling around four other Cabinet members — over similarly expensive or unusual travel — have only heightened the cynicism. Details emerged Friday on a trip that Veterans Affairs Secretary David Shulkin took to Europe in July; in between meetings with Danish and British officials, he and his wife went to the Wimbledon tennis match and took a cruise on the Thames. The government paid for their flights and some expenses.

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In a sharply worded memo on Friday, White House Office of Management and Budget Director Mick Mulvaney informed the heads of all executive departments and agencies that they should severely restrict the use of non-commercial travel and will now need advance approval from the White House chief of staff in most instances.

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“Every penny we spend comes from the taxpayer,” Mulvaney said. “Accordingly, with few exceptions, the commercial air system used by millions of Americans every day is appropriate, even for very senior officials.”

Price, a Georgia multimillionaire and orthopedic surgeon by training, had announced Thursday that he would reimburse the government for a fraction of the costs of his charter flights in recent months. An HHS official said Price would write a check for $51,887.31, which appears to cover the cost of his seat on the flights but not those of his staffers.

Politico, which first reported on Price’s repeated use of private planes, has estimated the total expense of the taxpayer-funded trips exceeded $400,000 — and it reported early Thursday evening that his White House-approved travel on military planes to Africa, Europe and Asia cost more than $500,000.

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After the HHS inspector general initiated a probe, Price first said he would suspend such trips until the inquiry was complete. On Thursday he pledged to no longer take such flights, saying he regretted “the concerns this has raised regarding the use of taxpayer dollars.”

But Trump had also directed some of his frustration at Price over the inability of Republicans in Congress to pass a health-care replacement bill. House Speaker Paul D. Ryan (R-Wis.) and former House speaker Newt Gingrich of Georgia had pushed for the then-congressman to lead HHS, arguing that Price’s medical and policy expertise and congressional ties could help Trump deliver on his vow to repeal the Affordable Care Act.

During a speech in July to a gathering of Boy Scouts, Trump said — jokingly at the time — that Price could lose his job if a bill didn’t pass.

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“He better get the votes,” Trump said. “Otherwise I will say, ‘Tom, you’re fired.’ ”

Several congressional Republicans praised Price on Friday: Ryan called him “a good man. He has spent his entire adult life fighting for others, first as a physician and then as a legislator and public servant. He was a leader in the House and a superb health secretary.”

The ruckus prompted by the secretary’s travel habits followed complaints earlier this year by Democrats and other critics about his ethics for a separate reason: private investments he made while a House member in health-care companies that could have benefited from bills that he sponsored.

At his confirmation hearing in late January, the Senate Finance Committee’s senior Democrat, Sen. Ron Wyden (Ore.), accused the nominee of “a conflict of interest and an abuse of position.” The main focus of such criticism involved Price’s largest stock purchase in 2016 — between $50,000 and $100,000 — in an Australian biomedical firm called Innate Immunotherapeutics.

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The investment coincided with final negotiations on the sweeping 21st Century Cures bill, aimed in part at helping to accelerate clinical trials and approval of drugs like Innate’s.

Price acknowledged that the purchase, and several smaller ones he’d made in the company the previous year, occurred without an investment broker. As part of his confirmation, he testified before members of the Senate Health, Education, Labor and Pensions Committee that he had learned of the company from a House colleague, Rep. Chris Collins (R-N.Y.), an Innate board member. He contended that he received no insider information ahead of time.

Sen. Patty Murray (Wash.), the HELP Committee’s top Democrat, reacted to Price’s departure Friday by focusing on “the serious, unanswered questions about improper financial benefits.” She also faulted his approach to health care as “ideologically driven,” particularly on women’s health and reproductive rights.

“The fact that this decision took this long only indicates the extent to which the Trump Administration allows its senior officials to put themselves, and partisan politics, ahead of families and communities,” Murray said in a statement.

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Other criticism of Price revolved around his uncommon reliance on campaign contributions from the health-care industry. During his 2016 campaign for a seventh House term, he accepted more than $700,000 from physicians, hospitals, drug companies and health insurers, according to the Center for Responsive Politics.

Price’s views — abhorring the ACA and other forms of what he regards as government intrusion into health care — fit neatly within the Trump administration’s orthodoxy. Yet the secretary arrived at the helm of HHS holding a variety of views that deviate from the basics of federal health policy.

He is a longtime member of an alternative medical group called the Association of American Physicians and Surgeons, which opposes Medicare, the highly popular government insurance for older Americans, and offers training to doctors on how to opt out of the program. The group also opposes mandatory vaccination as “equivalent to human experimentation,” a stance contrary to requirements in every state and recommendations of major medical organizations and the federal Centers for Disease Control and Prevention.

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In public speeches in the years before he became secretary, Price deplored HHS’s Centers for Medicare and Medicaid Services — a key agency within the department he would run.

Price as a congressman supported policies that favored his fellow physicians. He championed tighter limits on medical malpractice cases against doctors.

It is unclear whom Trump will tap to lead one of the largest agencies in the federal government. Both Seema Verma, administrator of the Centers for Medicare and Medicaid Services, and Scott Gottlieb, who heads the Food and Drug Administration, are well-liked and respected within the White House. But neither has the kind of political experience that many previous secretaries had before taking of the post.

Former Louisiana governor Bobby Jindal, another Republican whom Price edged out for the job during the transition, could be in the mix, as well as possibly Sen. Bill Cassidy (R-La.).

Regardless of who is nominated, Republican health expert Avik Roy said in a email that the administration’s policy objectives will remain unchanged. “President Trump has pledged to repeal and replace Obamacare, and I’m sure he will continue to take that pledge seriously,” Roy said.

Wright, the new acting secretary, trained as a physician and public health specialist and focused on family medicine and preventive care. Before arriving at HHS about a decade ago, he had extensive experience in occupational health. In response to the 9/11 terrorist attacks and Hurricane Katrina, he convened conferences designed to improve hospitals’ preparation for various kinds of disasters.

A career official, thought to be more Republican than Democrat, Wright had prominent roles in both the George W. Bush and Obama administrations. He is considered to be someone who knows HHS operations and has served in prior situations as a competent, interim executive, according to one longtime public health official.