Five people have died after a car which had earlier been pursued by police crashed head-on with another vehicle on the M4.
The Independent Police Complaints Commission (IPCC) will investigate the crash, at 0320 BST at Newport.
Police said officers stopped following the car before it turned onto the motorway in the wrong direction.
Three men died at the scene and a fourth is in a critical condition. A couple in the second car also died.
The four men were travelling in a red Ford Mondeo and the couple in a red Volvo 940.
The 18-year-old survivor suffered multiple fractures and is at the Royal Gwent Hospital, Newport.
It has been reported in Ireland that the couple were in their 60s and came originally from County Mayo in the Irish Republic, but had been living in England.
There were seven-mile tailbacks on the M4
It is believed they had been to Ireland to visit family and were driving home after getting off the Rosslare to Fishguard ferry when the crash happened.
The collision happened on the eastbound carriageway between junctions 25 and 24.
Some time before, police said there had been an "incident" at nearby Penhow, when police tried to stop a car.
A Gwent Police spokeswoman said: "The force had cause to attempt to stop a vehicle on the A48, after it was made aware of suspicious activity.
"A short pursuit ensued and, as confirmed in the IPCC's earlier press release, when the other vehicle entered the M4 in the wrong direction, the Gwent Police traffic car halted this pursuit."
She added: "Gwent Police offers its sincere condolences to the families of all the deceased following this terrible tragedy and will continue to work closely with the IPCC in support of their investigation."
The IPCC appealed for information from anyone who saw a red Ford Mondeo travelling the wrong direction eastbound carriageway on the M4 near the Christchurch Road motorway bridge at about 0315 BST.
An 18-year-old man has been taken to hospital
IPCC commissioner Tom Davies said: "It has emerged that at around 0300 this morning a marked police vehicle had reason to try and stop a car containing four male occupants.
"Early indications are that the vehicle being pursued took a turn onto the motorway in the wrong direction.
"The police vehicle did not follow it. Some one-and-a-half miles down the motorway, the fatal collision occurred."
The M4 later reopened in both directions.
Police said the identification of those killed was "currently being ascertained and their families informed".
The westbound side of the motorway was reopened some seven hours after the crash and the eastbound side reopened an hour later.
Monday morning rush hour traffic tailed back for up to seven miles, with all main roads across south east Wales heavily congested.
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.
Witnesses are asked to call the IPCC on freephone 0800 096 9076 or email firstname.lastname@example.org