Route 16 was closed after a car crashed as it was being pursued by police on Thursday afternoon.
The road was shut down between Flat Brook Road and Route 149 in East Hampton, near the Colchester line.
Police received several 911 calls about an Eagle Talon driving recklessly between Portland and East Hampton for more than an hour.
Police began a pursuit. The driver, James Millell of Middletown, hit an animal control officer's vehicle and two other cars before his car slammed into a guardrail around 3 p.m., according to the East Hampton police chief.
Two Lifestar helicopters were called to fly Millell and his female passenger to the hospital with serious injuries. Both were inside the vehicle that crashed.
The car had out-of-state plates, according to police.
Route 16 reopened around 6:45 p.m.