President Barack Obama was being kept up to date by his homeland security and counterterrorism aide on what Florida officials are investigating as a terrorist attack.
FBI official Ronald Hopper told reporters officials were "confident" there was no immediate further threat to the area, or to the United States. Because of the scale of the crime, however, Orlando's mayor declared a city-wide state of emergency and has asked the Florida governor to take the same measure state-wide. The federal government has offered its full support with the probe.
Police have yet to officially identify the gunman but television networks quoting law enforcement sources named him as Omar Mateen, who was born to Afghan parents in 1986 and lives in Port St Lucie, Florida, about two hours drive from Orlando.
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CBS News reported that Mateen -- who died in a shootout with police after the siege -- has no apparent criminal history.
Hopper said authorities were looking into whether the suspect had "leanings" toward Islamic extremism, but Florida officials also invited a local Islamic leader to address the media in a bid to preempt a possible backlash against the Muslim community.
- 'Rescue hostages' - The chaotic events unfolded over a three hour period, beginning at around 2 am when shots rang out amid the throbbing music at the Pulse Orlando nightclub near closing time.
Police said the shots were fired by a gunman armed with an assault rifle and a handgun.
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A police officer working "extra duties" at the club responded, joined by two other officers, who engaged the suspect in a gun battle, Orlando police chief John Mina said.
"The suspect at some point went back inside the club where more shots were fired. This did turn into a hostage situation," he told reporters.
"At approximately 0500 hours this morning, the decision was made to rescue hostages that were in there."
Police then stormed the venue, using explosives and breaking through a wall with a wheeled armored vehicle known as a BearCat. Mina said about 30 people were rescued during the operation.
It was unclear whether all the victims were killed by the gunman or if some died in the ensuing shootout with police.
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The attack coincides with gay pride month in the United States, with festive marches and events being held all over the country including in Orlando last week.
It was the second shooting incident in the city in just over 24 hours, coming shortly after singer Christina Grimmie was shot dead late Friday by a gunman who stormed a theater where she had just finished a gig.Mina said there was no indication of a link between the two shootings.