The collision happened at about 6.35am on the A75 at Skyreburn, Dumfries and Galloway.
The man was pronounced dead at the scene of the crash, which forced the closure of the road.
Other people who were injured in the crash have been receiving treatment. It is not yet known how many people were hurt in the incident.
Police Scotland said the road would remain closed for a considerable time to allow a full crash investigation to take place.
Lengthy diversions have been put in place and motorists were asked to avoid the area.
Elsewhere, a 36-year-old man died after his car went down an embankment in the Highlands.
Police were called to the scene of the crash, on the A82 around one mile south of Spean Bridge at about 9pm yesterday.
Officers found that the silver northbound vehicle had come off the road and gone down an embankment into trees. The driver was the only person in the car.
The road was closed for about seven hours while an investigation was carried out.