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Another 14 people were wounded at the Inland Regional Center in San Bernardino, police said.
It appeared to be the worst mass shooting since the December 2012 slaughter of 20 first-graders and six staffers at the Sandy Hook Elementary School in Newtown, Conn.
"These people came prepared to do what they did as if they were on a mission," said San Bernardino Police Chief Jarrod Burguan said. "They were armed with long guns, not with handguns."
Burguan added "the suspects have fled."
Burguan warned that the death toll could climb as they continue to search the building. "This is a tragedy," he said.
"We don't know if this is a terrorist incident," added David Bowdich, the FBI assistant director in Los Angeles.
Neither Burguan nor Bowdich would confirm reports that at least one of the suspects was believed to be wearing tactical gear.
While law enforcement briefed reporters inside the state facility, firefighters set up a triage area outside the complex on South Waterman Avenue, where they were treating the wounded on the street and loading others into waiting ambulances for treatment at nearby Loma Linda Medical Center.
Some were transported in the back of pickup trucks.
Meanwhile, all San Bernardino city buildings, the courthouse, and all the county buildings were placed on blockdown.
President Obama was briefed by Homeland Security Advisor Lisa Monaco and asked to be updated as the situation develops, a White House official said.
"Absolutely heartbreaking," California Sen. Dianne Feinstein tweeted.
The first shots were fired at the center around 11 a.m. local time (2 p.m. ET), said Lawhead.
Marybeth Feild, president of the center's board of trustees, said she heard from staffers that the gunfire erupted in a conference center.
"That's where the shooting took place," she told NBC News. "I was going to a meeting today, but I wasn't there myself."
Feild said a group of some kind was holding a meeting in conference area "and that's where we're hearing the shooting went into."
"We often let other groups rent out the space," she added. "I'm not sure who was renting it out today, but I believe it was a healthcare event."
Outside, the normally tranquil suburban streets were jammed with police vehicles and first responders.
Dozens of SWAT team officers massed outside the facility while police evacuated the occupants who filed out with their hands up.
Police also cleared out nearby buildings and marched the occupants out of harm's way to a nearby golf course.
In addition to the FBI, federal ATF agents were also on the scene, officials said. So was the bomb squad.
"There were some things that were in the building that were not immediately identifiable that caused us concerns," Burguan said.
Jim, a sales person at the nearby Structural Material Company who did not give his full name, told NBC News the neighborhood was an armed camp.
"There's plenty of police activity," Jim said. "A lady ran into our bathroom and said somebody was shooting there."
Jim said police told him and the staff — about 10 to 12 people — to stay inside the building, which is about 200 to 300 yards from the Regional Center, a state-run center for people with developmental disabilities.
The mayhem in California came just days after a gunman barged into a Planned Parenthood facility in Colorado Springs, Colo., killing three people during a five hour siege.
Democrat Hillary Clinton was the first of the presidential candidates to weigh in on the unfolding tragedy.
"I refuse to accept this as normal," she tweeted. "We must take action to stop gun violence now."
She was followed by Democratic rivals Martin O'Malley and Bernie Sanders, and Republican presidential candidates Donald Trump. Ben Carson, Ted Cruz, Jeb Bush, John Kasich, George Pataki, Lindsey Graham, Chris Christie and Mike Huckabee.
"California shooting looks very bad," Trump tweeted. "Good luck to law enforcement and God bless. This is when our police are so appreciated .