Suffolk Police officers were called to Bury Road in Ipswich at about 09:35 GMT after a VW Golf and a Rover 75 collided on a roundabout near a supermarket.
They said the Golf driver, believed to be in his 70s, may have become ill just before the crash.
The Rover driver was airlifted to Addenbrooke's Hospital in Cambridge with serious injuries.
A female passenger in the Golf was taken to Ipswich Hospital with chest pains.
Police are appealing for witnesses.
A man died in a two-car crash after suffering what police believe was a "medical episode" at the wheel.