The Highways Agency says the M1 southbound entry slip road at junction five is expected to re-open at 11am.
Police said two men travelling in a second BMW are being treated in Watford General Hospital, although their injuries are not thought to be life-threatening.
An investigation is now under way to determine the cause of a crash on the M1.
The accident closed five junctions of the motorway in both directions - although the northbound carriageway has since reopened.
Two men have been killed in a crash on the M1 which closed a section of the motorway this morning, police said.
The collision near Watford in Hertfordshire between two black BMW cars happened shortly before 2.40am on the southbound carriageway between junctions five and four.
A male driver and his front seat passenger were killed, while another two male passengers in the car were taken to St Mary's Hospital in Paddington, central London, with "serious injuries", a Hertfordshire Police spokeswoman said.
Police said the M1 southbound between junctions 5 and 4 remains closed and urged drivers to use alternative routes.
Drivers should use either the A1 or M40/A40.
Officers were called to a serious collision at around 2.40am after a crash between two vehicles.
The southbound carriageway will be closed until at least mid-morning while police continue their investigation.
The northbound carriageway was closed but has been re-opened.
M1 southbound (5-4) closed following serious collision. Pls use A1 or M40/A40 http://t.co/qfqBPXIR
The northbound carriageway between junctions one and five, from London to Watford, has now reopened after a serious collision, Hertfordshire Police said.
The southbound carriageway is still closed between junctions four and five, between Edgware and Watford.
It is expected to be closed until at least mid-morning, a police spokeswoman added.
The M1 is closed in both directions near Watford in Hertfordshire due to a serious road traffic collision, the Highways Agency has said.
The northbound carriageway is closed between junctions J1 and J5
The southbound carriageway is closed between junctions J5 and J4
Motorists have been advised that the closures are likely to be in place through the morning peak period and to consider alternative routes for their journeys into London or to delay where possible.