The crash happened about 7:30 a.m. at the intersection of Arlington and Stover avenues, according to the Riverside Fire Department.
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According to investigators, the driver of a white Honda sedan was heading westbound on Arlington Avenue when it collided with a grey Nissan Sentra traveling eastbound.
The driver of a white Honda was taken to the hospital in serious condition, according to authorities.
Investigators said there were a total of four people in the Sentra, including three children.
A spokesperson for the fire department could not confirm the ages of the victims or whether any of them were ejected from the two sedans.
All four people in the Sentra remain hospitalized in conditions ranging from serious to critical, according to authorities.
News video from the scene showed debris from the wreckage scattered across Arlington Avenue.
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The impact of the crash left both vehicles mangled.
An engine block from one of the cars was seen on the ground near curb. Also on the street were one of the car's two front wheels and axle, which were separated from the chassis.
Residents who live in the area told Eyewitness News they see scenes like this quite often.
"At least twice, three times a month, there's an accident," said Edward Viramontes. "Especially my block ... they almost ran me over like twice, just this week."
The cause of the collision remains under investigation.