Fifty people are now known to have died in Saturday's shooting in a gay nightclub in Orlando, Florida, and a "state of emergency" has been declared, the city's mayor Buddy Dyer has said.
The gunman, named by officials as 29-yr-old Omar Mateen, was killed after taking hostages. Another 53 people were injured in the shooting at the Pulse club.
Officials said the killings were likely to be ideologically motivated, though there was no information that the gunman was associated with a particular group.
However, US Congressman Alan Grayson said it was "no coincidence" the attack happened in a gay club.
It is believed that the suspect, who comes from the Florida town of Port St Lucie and is of Afghan descent, was not on a terrorism watch list, although he was currently being investigated for an unrelated criminal act.
Relatives have been gathering at local hospitals desperate for news of their loved ones.
Many had received calls and texts from loved ones inside the club as the siege began, and some have heard nothing since.
The death toll given by Mayor Dyer means that the Orlando attack surpasses the 2007 massacre at Virginia Tech which left 32 people dead.
"Today we're dealing with something that we never imagined and is unimaginable," he said, adding that there was "an enormous amount of havoc" and "blood everywhere".
Orlando Police Chief John Mina said the attack began at 02:00 (06:00 GMT). There was an exchange of fire with a police officer working at the club, but it is unclear whether that was inside or outside the venue.
After this a "hostage situation" unfolded, he said.
Chief Mina said a decision was taken at 05:00 to send a police assault team into the club after receiving texts and phone calls from some of the hostages.
"Our Swat officers exchanged gunfire with the suspect, the suspect is dead," he said.
"He appeared to be carrying an assault-type rifle and a handgun, and had some type of device on him."
A bomb squad robot has been searching the scene for possible booby traps.
According to the Mass Shooting Tracker, the US last year suffered 372 mass shootings, defined as a single incident that kills or injures four or more people. Some 475 people were killed and 1,870 wounded.
The latest incident came as Orlando was still reeling from the fatal shooting on Friday night of 22-year-old singer Christina Grimmie following a concert in the city.
Worst US mass shootings in last 25 years
-At least 50 dead, 2016 - Omar Mateen opens fire on revellers at gay club in Orlando, Florida
-32 dead, 2007 - Student Seung-Hui Cho massacres students at Virginia Tech university before killing himself
-27 dead, 2012 - Adam Lanza kills 20 six- and seven-year-old children and six adults before killing himself at Sandy Hook, Connecticut
-23 dead, 1991 - George Hennard drives through the wall of a cafe in Killeen, Texas, before opening fire and committing suicide
-14 dead, 2015 - Syed Rizwan Farook and Tashfeen Malik open fire at a staff gathering in San Bernardino
-13 dead, 2009 - Maj Nidal Malik Hasan opens fire at army base in Fort Hood, Texas
-13 dead, 2009 - Jiverly Wong shoots people at New York immigrant centre before killing himself
-13 dead, 1999 - Eric Harris and Dylan Klebold kill fellow students and a teacher at Columbine High School in Littleton, Colorado
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