Emergency services are attending the scene of "serious accident" on the A26.
The road is closed in both directions from the Barcombe turn off to Isfield Road following the crash involving a van and a car.
Police, ambulance crews, and firefighters were seen at the scene of the collision near an Esso garage.
Accident investigators are also understood to be at the scene.
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The 28 and 29 bus routes towards Lewes, Uckfield and Tunbridge Wells are being diverted via Nevill Road and Offham Road.
The Argus understands that the road will remain closed for most of the evening.
Sussex Police has been approached for comment
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