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.
