Drivers are being warned to avoid the M4 junction 17 at Chippenham after a double fatal collision closed the motorway in the westbound direction this morning.
The outside lane of the eastbound carriageway is also closed.
The crash, involving a lorry and a van on the slip road close to junction 17, happened at just after 4.30am
Two men travelling in the van were pronounced dead at the scene and two other men, also travelling in the van, have been taken to Southmead Hospital in Bristol with serious injuries.
A fifth male travelling in the van has been taken to the Great Western Hospital in Swindon with less serious injuries.
The lorry is on the hard shoulder but the van is facing the wrong direction in the outside lane.
Traffic is building up in Chippenham and there are severe delays on the A350, especially where there are roadworks on the Morrisons roundabout.
A police spokesman said: "Motorists are being asked to avoid the motorway if possible as queues of traffic are now building up around junction 17 for Chippenham.
"The road is likely to remain closed for the next hour or so while debris is cleared from both sides of the carriageway."
"Roads in the villages don't seem to be affected yet but there are big queues on the bypass."
Anyone who saw the crash can contact police on 101 or Crimestoppers on 0800 555 111.