Two people suffered serious injuries in a crash on the A27 Brighton bypass at about 7.15am today.
The crash happened on the westbound stretch of the road between Falmer and Hollingbury and involved a skip lorry and a van.
An air ambulance attended as one casualty was taken to hospital in London and the other to the Royal Sussex County Hospital in Brighton.
A third person suffered less serious injuries.
The road was closed in both directions during the morning rush-hour with tailbacks said to be stretching for seven miles at one point.
Sussex Police advised drivers to avoid the area.
The eastbound side of the road reopened just before 9am but westbound traffic was still queuing beyond the Lewes bypass as far back as the Beddingham roundabout.
Drivers heading out of Brighton on the A270 Lewes Road through Moulsecoomb and those trying to join the A27 from Coldean and Woodingdean were also affected.