The crash, which also involved a third vehicle, happened around 2 p.m., according to Contra Costa County Fire Protection District Spokesperson Steve Hill.
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The road south of Camino Diablo was still shut down in both directions just after 3 p.m. Hill said at least two helicopters and multiple ambulances were necessary to transport victims.
The initial report said a van collided head-on with a pickup truck. A public information officer with Con Fire originally told ABC7 News 10 people were injured, but that has since been corrected.
Two people had to be extricated from the vehicles; one at 2:30 p.m. and the other at 2:47 p.m.
The victims were transported to John Muir Medical Center in Walnut Creek, including a 31-year-old man and a 40-year-old.
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Hill said it's likely the road will remain closed into the evening commute.
This story is developing. Check back for updates.