The crash was reported at about 8:20 a.m. on Highway 12 east of Kirkland Ranch Road, near American Canyon, CHP Officer Jaret Paulson said.
Paulson said the people who died were two men and two women in a Subaru Forester. Their names have not been released but Paulson said their ages range from about 20 to 80.
He said a big-rig was traveling west on Highway 12 behind the Subaru and a commercial truck just before the accident happened, Paulson said.
Traffic began to slow or stop, and the big-rig did not stop in time and crashed into the back of the Subaru, pushing it into oncoming traffic and into the path of an eastbound big-rig, he said.
The eastbound big-rig struck the Subaru, pushing it about 200 feet up the road before it came to a stop.
Four occupants of the Subaru were pronounced dead at the scene.
The driver of the big-rig involved in the initial collision was transported to a hospital with minor to moderate injuries, Paulson said.
That big-rig also clipped the commercial truck before coming to rest, but the driver and passenger in the truck were uninjured, he said.
The driver of the eastbound big-rig was also unhurt.
Highway 12 was still shut down between Kelly Road and Interstate Highway 80 at midday but the CHP expected to reopen the roadway shortly after 1 p.m.
