Police are hunting two young men who were spotted fleeing from one of the cars.
A 74-year-old woman had to be cut free from the wreckage of one car after the crash in Southey Green yesterday.
The pensioner was taken to hospital with what police said were believed to be serious head injuries.
A man in his 70s who had been travelling in the same vehicle was also taken to hospital in a serious condition.
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Police have appealed for witnesses after two young men were seen getting out of the other vehicle and fleeing.
Emergency services were called to the scene in Southey Green Road, near the junction with Dryden Way, at around 12.05pm.
Police said a blue Ford Focus was travelling towards Southey Green along Southey Green Road and is thought to have been overtaking a JCB when it collided with a red VW Golf travelling in the opposite direction.
Two people in the Focus were taken to hospital with injuries police said were believed to be serious.
Acting Police Sergeant Mark Bradey said: “We believe two young male occupants from the red Golf fled the scene.
“We’re eager to speak to anyone who saw the collision happen or who believes they have seen either of the males.”
Mr Bradey said the men had initially run downhill, according to witnesses, before turning back and heading uphill.
A bystander said the Ford Focus had been overtaking the JCB when it collided with the Golf head on.
Firefighters removed the Ford’s roof to free the woman.
n Anyone who thinks they may be able to help is asked to call police on 101, quoting the incident number 361 of January 12.