Leading Republican presidential nominee Donald Trump has said he was "right on radical Islamic terrorism" and has called for toughness and vigilance.
Trump made the statement on Twitter after the attack in an Orlando, Florida nightclub which killed 50 people and wounded 53.
"Appreciate the congrats for being right on radical Islamic terrorism, I don't want congrats, I want toughness & vigilance," Trump tweeted. "We must be smart."
The Orlando shooter, who was killed by police, was identified as a Florida resident, Omar S. Mateen.
An FBI official said Mateen might have leanings toward Islamic State's ideology but cautioned that the suspected Islamist connection required further investigation.
Trump has proposed a temporary ban on Muslim immigration to the United States as a way to combat the threat of radical Islamist attacks.
In the wake of the deadliest shooting in US history, President Barack Obama has addressed the nation, calling the attack an act of terror.
He has given more than a dozen addresses following a mass shootings in his seven years as President.
"We know enough to say this was an act of terror and an act of hate," he said.
"The FBI is appropriately investigating this as an act of terror. We will go wherever the facts lead us... What is clear is he was a person filled with hatred."
Democratic presidential-hopeful Hillary Clinton expressed her support for the LGBT community.
"We will keep fighting for your right to live freely, openly and without fear. Hate has absolutely no place in America," she said.
She also issued another call for gun control laws, saying: "We need to keep guns like the ones used last night out of the hands of terrorists or other violent criminals."