"For now, we can say for certain that we need to redouble our efforts to defend our country from threats at home and abroad," Clinton said. "That means defeating international terror groups, working with allies and partners to go after them wherever they are, countering their attempts to recruit people here and everywhere, and hardening our defenses at home. It also means refusing to be intimidated and staying true to our values."

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But while Clinton and other Democrats spoke of the need for further firearms restrictions and decried the targeting of members of the gay, lesbian, bisexual and transgender community, Republicans emphasized the threat homegrown terrorism poses in the United States.

But several Republicans, including presumptive GOP presidential nominee Donald Trump, said the shooting underscored how the federal government has not done enough to curb the threat of terrorism. Most Republican officials did not mention that the gunman targeted a gay nightclub.

Trump, who tweeted that it was “horrific” and he was “praying for all the victims & their families,” also questioned why it had not been prevented. “When will this stop? When will we get tough, smart & vigilant?” he tweeted. An hour later, he reiterated his criticism of the administration's national security stance.

About an hour after that, Trump called some attention to his own warnings about terrorism, tweeting: "Appreciate the congrats for being right on radical Islamic terrorism, I don't want congrats, I want toughness & vigilance. We must be smart!"

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Later, Trump tweeted that President Obama should "immediately resign in disgrace" if he did not mention the words "radical Islamic terrorism."

Sen. Marco Rubio (R-Fla.) said in a statement that he and his staffers were prepared to offer constituent services for those affected by the attack, but emphasized government officials must focus on stamping out domestic terrorism wherever possible.

He headed to Orlando Sunday afternoon. “Confronting the threat of violent homegrown ‎radicalization is one of the greatest counterterrorism challenges our law enforcement and intelligence community faces,” Rubio's statement said. ‎“We must do more at every level of government and within our own communities to identify and mitigate this cancer on our free society and prevent further loss of innocent life."

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Speaking to reporters at the White House, Obama called on Americans not to "give into fear or turn against each other" even as authorities investigated what they are treating as a domestic terror incident.

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The president described the attack as "a sobering reminder that attacks on any American — regardless of race, ethnicity, religion or sexual orientation — is an attack on all of us and on the fundamental values of equality and dignity that define us as a country."

As the federal probe got underway, politicians suggested that the underlying motive would probably ignite a new debate on at least one of several hot-button topics: gay rights, terrorism or gun control.

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“Our hearts ache for all those killed in this senseless attack, and we pray for the swift recovery of all those who were wounded,” said House Minority Leader Nancy Pelosi (D-Calif.). “While many questions have yet to be answered, the pain of this attack in a mainstay of the Orlando LGBT community is surely magnified as our nation celebrates LGBT Pride month.”

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Sen. Tammy Baldwin (D-Wis.), the only openly gay U.S. senator, posted on Facebook: "This was not only a horrific attack on the LGBT community, it was an attack on the freedoms we all hold dear."

Sen. Chris Murphy (D-Conn.) said shootings such as the one in Orlando are part of an “epidemic” that “will continue without end if Congress continues to sit on its hands and do nothing, again.”

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“I know the pain and sadness that has brought too many communities — Newtown, Oregon, Aurora, San Bernardino, and now Orlando — to their knees, and I can only hope that America’s leaders will do something to prevent another community from being added to the list,” he said in a statement. “This phenomenon of near constant mass shootings happens only in America — nowhere else. Congress has become complicit in these murders by its total, unconscionable deafening silence.”

But others put the threat of domestic terrorism front and center in their comments.

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Sen. Bill Nelson (D-Fla.) said in a statement Sunday he believed the strike was linked to the Islamic State, the Mideast extremist group also known as ISIL or ISIL. "I have spoken with the FBI and there appears to be a link to Islamic radicalism. I have conferred with additional sources and they think there is likely a connection with ISIS," he said. "So as we all mourn the senseless loss of life and investigators continue to learn more, we must remain vigilant and remember that if you see something, say something.”

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Speaking on NBC’s “Meet the Press” with host Chuck Todd, Sen. Jeff Flake (R-Ariz.) noted that the ensuing public debate would be shaped by what spurred the gunman to act. Law enforcement officials and relatives have identified the suspect, who was killed by police, as 29-year-old Omar Mateen from Fort Pierce, Fla.

“If it is found out that this person was at least [inspired] by ISIS, then it’ll probably be a terrorism debate,” Flake told Todd. “If he wasn’t, it may be a gun debate. But you’re right, it seems to be one or the other.

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“A lot of us have been talking for quite a while in terms of background checks and tightening background checks, particularly as it pertains to those with mental illness,” Flake said. “And I think that that debate can and should go on as well as the debate on how to best protect us against those who were inspired or funded or directed by international terrorists.”

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Sen. Bernie Sanders (Vt.), whose record on gun safety legislation came under attack during the Democratic presidential primaries, said later on the same show that the shooting provided yet another reason to revisit current laws. “I believe that in this country we should not be selling automatic weapons, which are designed to kill people,” Sanders said. “We have got to do everything that we can on top of that to make sure guns do not fall into the hands of people who should not have them, criminals and people who are mentally ill. So, that struggle continues.”