The deadliest mass shooting in U.S. history is raising new questions about the safety of the homeland and shaking up the race for the White House.

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Shocking revelations that the shooter had been previously investigated by the FBI more than once have many asking whether the incident could have been prevented.

Fifty people were killed, including the gunman, and 53 were wounded or injured in the attack early Sunday morning.

The shooter, Omar Mateen, pledged allegiance to the Islamic State in Iraq and Syria (ISIS) before attacking Pulse, a gay nightclub in Orlando, with an assault rifle and a handgun.

The FBI said it had conducted three interviews with the 29-year-old, who was born in New York to Afghan parents, but determined he did not represent a threat.

Donald Trump Donald John TrumpUS reimposes UN sanctions on Iran amid increasing tensions Jeff Flake: Republicans 'should hold the same position' on SCOTUS vacancy as 2016 Trump supporters chant 'Fill that seat' at North Carolina rally MORE, the presumptive Republican presidential nominee, is citing the mass shooting to advance his argument that legal and illegal immigration are endangering U.S. security.

“We admit more than 100,000 lifetime migrants from the Middle East each year. Since 9/11, hundreds of migrants and their children have been implicated in terrorism in the United States," Trump said in a statement.

“Hillary Clinton Hillary Diane Rodham ClintonJeff Flake: Republicans 'should hold the same position' on SCOTUS vacancy as 2016 Momentum growing among Republicans for Supreme Court vote before Election Day Warning signs flash for Lindsey Graham in South Carolina MORE wants to dramatically increase admissions from the Middle East, bringing in many hundreds of thousands during a first term — and we will have no way to screen them, pay for them, or prevent the second generation from radicalizing.”

Trump, who has been going through one of the rockiest periods of his presidential campaign, had planned to give a speech on Monday focused on Hillary and Bill Clinton William (Bill) Jefferson ClintonDolly Parton remembers Ginsburg: 'Her voice was soft but her message rang loud' Sunday shows preview: Justice Ginsburg dies, sparking partisan battle over vacancy before election Calls grow for Biden to expand election map in final sprint MORE.

He announced Sunday that he would broaden the discussion to national security.

“We need to protect all Americans, of all backgrounds and all beliefs, from Radical Islamic Terrorism — which has no place in an open and tolerant society,” he said. “Radical Islam advocates hate for women, gays, Jews, Christians and all Americans. I am going to be a President for all Americans, and I am going to protect and defend all Americans. We are going to make America safe again and great again for everyone.”

The comments from Trump echoed statements he made after terrorist attacks last year in Paris and in San Bernardino, Calif.

After a Muslim couple opened fire on government workers in San Bernardino, Trump called for a temporary ban on all Muslim immigration to the United States. While that proposal came under criticism from many in Washington, it did not appear to hurt his campaign. If anything, they proved popular with Republican voters on his march to the nomination.

Clinton, meanwhile, called the Orlando shooting an act of terror and hate and said the U.S. must “redouble our efforts to defend our country from threats at home and abroad."

“The gunman attacked an LGBT nightclub during Pride Month. To the LGBT community: Please know that you have millions of allies across our country. I am one of them," Clinton said.

The former secretary of State also called for gun control, saying the U.S. needs to keep guns "like the ones used last night" out of the hands of terrorists and criminals.

"This is the deadliest mass shooting in the history of the United States, and it reminds us once more that weapons of war have no place on our streets," Clinton said.

President Obama vowed a full investigation into the attack in a statement from the White House. He and Clinton, the presumptive Democratic nominee for president, also announced they would postpone their first joint campaign appearance together, scheduled for midweek in Green Bay, Wis.

“In the face of hate and violence, we will love one another,” he said. “We will not give in to fear or turn against each other. Instead, we will stand united as Americans to protect our people and defend our nation, and to take action against those who threaten us.”

The president said the shooting is a “sobering reminder that attacks on any American, regardless of race, 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.”

Trump ripped Obama for not labeling the attack as radical Islamic terror.

“In his remarks today, President Obama disgracefully refused to even say the words 'Radical Islam'. For that reason alone, he should step down,” Trump said. "If Hillary Clinton, after this attack, still cannot say the two words 'Radical Islam' she should get out of this race for the Presidency.”

An official said the FBI first became aware of Mateen in 2013 when he made "inflammatory comments to coworkers alleging possible terrorist ties."

In the course of that investigation, Mateen was interviewed twice, but the FBI was unable to verify the substance of his comments.

The FBI interviewed Mateen again in 2014. In that investigation, the FBI was looking into possible ties between Mateen and an American suicide bomber. The FBI determined that the contact did not constitute a threat at the time.

Before the attack on the Pulse nightclub, Mateen called 911 and pledged allegiance to ISIS. The terror group subsequently claimed responsibility for the attack, saying over an encrypted phone that it was carried out by one of its fighters.

Mateen was killed in a confrontation with police after a three-hour standoff involving hostages.

Other Republicans used forceful language in describing a war with Islamic terror groups, but stopped short of blaming immigration policies or ripping Obama and Clinton.

Speaker Paul Ryan Paul Davis RyanKenosha will be a good bellwether in 2020 At indoor rally, Pence says election runs through Wisconsin Juan Williams: Breaking down the debates MORE (R-Wis.), who criticized Trump’s remarks about an American-born judge of Mexican heritage overseeing a case against Trump University as “textbook” racism, said the U.S. needs to be “clear-eyed about who did this.”

“We are a nation at war with Islamist terrorists. Theirs is a repressive, hateful ideology that respects no borders,” he said. “It is a threat to our people at home and abroad. Our security depends on our refusal to back down in the face of terror. We never will.”

Sen. Ted Cruz Rafael (Ted) Edward CruzVideo of Lindsey Graham arguing against nominating a Supreme Court justice in an election year goes viral Sunday shows preview: Justice Ginsburg dies, sparking partisan battle over vacancy before election Democrat on Graham video urging people to 'use my words against me': 'Done' MORE (R-Texas) called for unity in the fight against radical Islamic terrorism.

“Enough is enough. What we need is for every American — Democrat and Republican — to come together, abandon political correctness, and unite in defeating radical Islamic terrorism,” the former presidential contender said in a statement.