The Independent Police Complaints Commission (IPCC) has been called in after a collision on the M4 at Newport in which five people died.
A sixth person suffered multiple injuries in the crash at 0320 BST which has shut the motorway both directions from junction 24 to 28.
Three young men in one car died at the scene and a fourth is in hospital, the Welsh Ambulance Service confirmed.
A couple - a man and a woman in the second car - also died at the scene.
The collision between a Red Ford Mondeo and a Red Volvo 940 happened happened on the eastbound carriageway between junctions 25 and 24 in Newport.
The IPCC has said it has been asked to carry out an investigation.
Gwent Police have said the M4 will be closed for some time
A spokesman said: "I can confirm that Gwent Police have referred the incident to us.
"I haven't got any further details but I know it is on the grounds that, prior to the incident, there was some form of police involvement."
A spokesman for Gwent Police said the identification of those killed is "currently being ascertained and their families informed".
It is thought the M4 will remain closed for some time between J24 (Coldra) and J28 (Tredegar Park) eastbound and J24 and J26 (Malpas Road) westbound.
There are currently tailbacks of up to five miles.
A police spokesman said: "Every effort is being made to open up the carriageways of the M4 as soon as possible."
Westbound traffic is being diverted off at Junction 24. Eastbound traffic is being taken off onto the distributor road at J28. Seven mile tailbacks are reported back to J30 (Cardiff Gate).
There is also heavy traffic on all main roads around the motorway.
Last month the M4 was closed around Newport for many hours after a lorry driver died in an accident at Tredegar Park.
At their worst, tailbacks for drivers after that crash reached 10-miles.
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