The 19-year-old man was apparently struck by an eastbound lorry on the A75 Gretna to Stranraer road in Dumfries and Galloway, police said.
The accident happened at about 2.40am today near Calgow Farm, about a mile east of Newton Stewart.
It forced the closure of the road for around seven hours to allow for collision investigations, with a lengthy diversion put in place. The road has since reopened.
The man is being treated in Dumfries and Galloway Royal Infirmary.
Police Scotland are asking anyone with information about the accident to come forward.
“Despite the late time of this collision, it is believed that a number of vehicles would have been in the area both before and after the incident,” the force said in a statement.
“Police have already stopped and spoken with a number of lorry drivers but we are appealing for anyone who has not already been spoken to who was in the area to contact them on the police non-emergency telephone number 101.”