Both directions of Hwy. 46 east of Highway 33 were closed for hours after the noontime crash. Traffic began flowing again just before 6 p.m.
The highway, which is northwest of Bakersfield, is a primary route to the central coast. Numerous crashes along 46 have earned it the nickname "blood alley."
Emergency crews said it appears that a Chevrolet Cavalier was traveling eastbound and passing big rigs when it crashed into a Toyota Prius.
An infant and the driver were reportedly killed in the Cavalier, and a man and woman were killed in the Prius. The names of the victims were released early Saturday by the coroner's office. The infant and driver in the Cavalier were identified as 1-year-old Nathaniel Sanchez and 25-year-old Jose Alberto Sanchez of Avenal. The Prius' driver was identified as 84-year-old Walter Elliott of Los Osos. 62-year-od Shirlene Ann Soto, also of Los Osos, was the right-front passenger who was also killed.
A 25-year-old woman from Avenal who was riding in the Cavalier was airlifted to Kern Medical Center with major injuries.
Traffic was being diverted onto Hwy. 33 using Brown Material Road while 46 remained closed.