The A9 was closed and diversions were put in place.
Three adults and a two-year-old boy were killed when two vehicles crashed and burst into flames on the main Perth to Inverness road in the Highlands.
A Dutch-registered Volvo estate and a pick-up truck collided on the A9 at The Slochd, north of Aviemore.
The crash, at about 1515 BST, also left a woman and a girl injured.
They were in the Volvo, along with a man who died and the boy. A man and a woman in the pick-up truck were killed, as were three of their four dogs.
The woman and girl were taken to Raigmore Hospital in Inverness.
The ambulance service said the woman had serious injuries, including suspected broken legs, but did not know the child's condition.
Eyewitness Ben Hayes, 34, described how he was almost caught up in the crash as the pick-up truck swerved towards him as he drove north with his partner and nine-week old baby.
He said: "It started to drift across the road so I pulled in as tight as I could. It hit the car behind us head on.
"I saw it in the mirror, and it burst into flames."
Warning to drivers
Chief Inspector Jim Neil said: "This was a horrific incident and our thoughts are with the families involved.
"It is important that we establish the cause of this terrible collision and I would appeal to all witnesses to come forward and contact police with any information that they might have.
"I would also add that this is a very busy time on the roads across the Highland area and there have been a number of collisions in recent days. It is imperative that people drive safely and with extreme caution."
Meanwhile, Northern Constabulary said an 83-year-old woman had died in a separate single-vehicle crash on the B9163 between Cononbridge and Culbokie on the Black Isle at about 1600 BST.
The A9 crash occurred on a stretch of single carriageway close to the Slochd summit.
Renewed safety calls
The road was closed for about seven hours but reopened before 2300 BST.
Parts of the A9 have a reputation as being among the most dangerous stretches of trunk road in the UK.
Last week, the deaths of Paul Anderson and his granddaughter Samantha Jane Carr at Dalwhinnie led to renewed calls for the A9 to be made a dual carriageway to improve safety.
Conservative MSP Murdo Fraser said there was a "compelling case" to upgrade the road.