Pra Loup - Tejay van Garderen pulled out of the Tour de France during Wednesday's 161km 17th stage from Digne-les-Bains to Pra Loup.
The 26-year-old American had been sitting third in the overall standings at 3:32 back from race leader Chris Froome.
But only 60km into the first Alpine stage of the race, Van Garderen started to struggle and lost touch with the peloton.
The BMC team leader, who was second to Froome in last month's Criterium du Dauphine, was suffering from headaches.
He dropped two minutes behind but his team-mates helped him back up to the peloton, only for an acceleration from Alberto Contador, who was fifth overall, to see Van Garderen dropped again and, with 70km still to ride, he climbed off his bike.
It means Spaniard Alejandro Valverde moves up into a podium position behind second-placed Nairo Quintana with Contador just 19 seconds behind.