The collision happened on the A82 north of Fort William, near the Brackletter Junction, at around 11.50am on Saturday.
The fire service, ambulance and police attended.
A Police Scotland spokesperson said: "Police Scotland can confirm there has been two fatalities. The road will remain closed for several hours to allow for accident investigation to take place.
"There is an alternative route for cars only, on the B8004 Gairlochy to Banavie Road."