Fire officials in San Bernardino said it was responding to a "20 victim shooting incident" and it was working to clear the scene.
It is still a "very active scene" and police are trying to secure the building, said a police spokeswoman.
There may be up to three gunmen, she said, and they were heavily armed and possibly wearing body armour.
She did not confirm the number of victims.
A local reporter tweeted that people are being evacuated from the Inland Regional Center, a non-profit medical and health organisation.
People are being seen wheeled away on stretchers with medics and police officers in attendance.
Representatives from the FBI and the Federal Bureau of Alcohol, Tobacco and Firearms are on the scene.
No arrests have been made yet.
An ABC affiliate tweeted that there are 12 fatalities, but police have not confirmed that number.