Two teenage girls and a driver in his 20s have been killed as the car they were in crashed into a tree.
West Midlands Police said officers had seen the vehicle moments before the crash in Kingswinford, near Dudley, but did not speak with the occupants or pursue it.
An air ambulance, a critical care car, three paramedic officers, an emergency doctor and six ambulances were sent to the scene, after being alerted by police at 8.54pm on Tuesday.
Those killed were pronounced dead at the scene, while two others, a teenage boy and a teenage girl also travelling in the yellow Skoda Fabia, are in a critical condition in hospital.
The families of all of those involved have been informed.
Confirming that the road had reopened after being closed overnight, Sergeant Dean Caswell said the inquiry was at an early stage.
He said: “This is a tragic time for the families of those involved, and we have specially trained officers who will be supporting them through the difficult time ahead.
“I’d urge anyone who saw the Skoda driving in the area last night, or who may have captured anything on dash-cam footage, to get in touch with us as soon as possible.”
A West Midlands Ambulance Service spokeswoman said the first resource on scene arrived three minutes after the call was taken.
The spokeswoman said: “Crews arrived at the scene to find a car had hit a tree, with five patients involved.
“Sadly, it soon became clear nothing could be done to save the driver of the car, a man, and he was pronounced dead at the scene.
“Despite best efforts of staff, two teenage girls who were back seat passengers in the vehicle were also confirmed deceased at the scene.
“The front seat passenger, a teenage boy, was treated for life-threatening injuries at the scene before being conveyed on blue lights and sirens to the Major Trauma Centre at Queen Elizabeth Hospital for further treatment.
“The final back seat passenger, a teenage girl, was treated for potentially life-threatening injuries and was also conveyed on blue lights and sirens to Queen Elizabeth Hospital in Birmingham for further treatment.
“Our thoughts go out to the families of all those involved at this time.”