Spaniard Alejandro Valverde pulled out of the Tour de France after breaking his collarbone on stage three.
The Illes Balears rider, 26, crashed 20km from the finish of the 216.5km run from Esch-sur-Alzette to Valkenburg after a pile-up in the peloton.
Valverde was one of the favourites for the Tour following the withdrawal of Jan Ullrich and Ivan Basso.
"I was just unlucky. All of a sudden someone braked and I couldn't avoid hitting the back wheel ahead," he said.
"I'm really disappointed, but I'm not devastated. I just want to get better and get back to racing as soon as possible."
Team-mate Oscar Pereiro, with whom Valverde collided, said: "This has destroyed all our hopes. We knew he could get a podium place and we thought he might win the race."
Valverde won one stage last year in Courchevel before pulling out three days later with a knee injury.
Dutch rider Erik Dekker and American Fred Rodriguez also withdrew after crashing.
"He's in pain and obviously bruised but the doctors feel he could still start"
Rabobank leader Dekker and Davitamon rider Rodriguez hit the pavement in the village of Verviers, 59 kms from the finish.
This year's Tour was due to be the last in 36-year-old Dekker's career.
Australian Stuart O'Grady is a doubt for the fourth stage after fracturing a vertebrae in his back.
A CSC team spokesman said X-rays had shown that O'Grady fractured a vertebrae in his lower back, but that a decision would be taken on Wednesday.
"Stuart has fractured it in a way that means he may still be able to race," team spokesman Bryan Nyygard.
"He's in pain and obviously bruised but the doctors feel he could still start."