Floyd Landis cracked after an attack from Carlos Sastre as Spaniard Oscar Pereiro reclaimed the Tour de France lead in a dramatic 16th stage.
Landis saw his hopes swept away
Dane Michael Rasmussen triumphed after a solo breakaway in the toughest stage of the race so far, also taking over the King of the Mountains jersey.
But the drama unfolded on the final climb as Sastre's surge sent Landis, whose hopes are over, back-pedalling.
Sastre is now second overall, 1:50 behind Pereiro, who finished third.
Landis struggled in more than 10 minutes behind Rasmussen and is now 11th overall, over eight minutes adrift of Pareiro.
The dramatic collapse of the Pennsylvanian overshadowed an incredible performance from Rasmussen, who won all four climbs over five-and-a-half hours of gruelling riding in sweltering heat.
The Rabobank rider broke away with Tadej Valjavec and Sandy Casar just 10km into the 187km stage from Bourg d'Oisans to La Toussuire.
He led them over the 2,642m Col du Galibier, the highest point of this year's race, before dropping Casar, then Valjavec on the second major climb, the Col de la Croix-de-Fer.
Rasmussen celebrates as he crosses the finish line
"I did the entire stage by myself about a month ago, and I knew what was coming up," said, Rasmussen, who is now 45 points clear of David de la Fuente in the polka-dot jersey.
"I was very disappointed how yesterday (Alpe d'Huez) went. I knew I could do a lot better and had a lot to prove to myself because 90% of my season happens on these three days in the Alps."
With Levi Leipheimer, who started the day six minutes and 18 seconds adrift of Landis, also breaking away, the leading group were forced to try to peg back the deficit.
Leipheimer had moved into second, still nearly five minutes behind Rasmussen, by the top of the third climb, the Col du Mollard.
But the American slipped back on the dramatic final climb up to the ski resort of La Toussuire, Sastre's savage burst taking most of the overall leaders with him, but not Landis.
It is like war out there. You have to attack when you can
Landis, who requires hip surgery after the Tour, initially kept pace with a Denis Menchov attack, aided by the T-Mobile team helping rival Andreas Kloden up the mountain.
But when Sastre leapt off the front of the leading group with 10km left, Landis - with no-one from his Phonak team to assist him - dropped back disastrously, seeing all his hard-earned advantage rapidly disappear.
"I saw Landis couldn't give any more so I went on the attack," said Sastre. "It is crazy - it is like a war out there. You have to attack when you can."
Sastre and Kloden, who are now second and third overall, pushed on to improve their chances of overall victory, but Pereiro's final sprint showed he cannot be discounted.
"We never reckoned on Landis struggling as he did," said Pereiro, who spent four years with the Phonak team before leaving last year.
"It was an important step for me today towards the yellow jersey, but Landis showed anybody can have an off-day."
Result of stage 15:
1. Michael Rasmussen (Den/Rabobank) 5 hours 36 mins 04 secs
2. Carlos Sastre (Spa/Team CSC) +1:41
3. Oscar Pereiro (Spa/Caisse d'Epargne) +1:54
4. Cadel Evans (Aus/Dav-Lotto)+1:56
5. Andreas Kloden (Ger/T-Mobile) +1:56
6. Christophe Moreau (Fra/AG2R)) +2:37
7. Pietro Caucchioli (Ita/C.A) +2:37
8. Cyril Dessel (Fra/AG2R) +2:37
9. Levi Leipheimer (USA/Gerolsteiner ) +3:24
10. Haimar Zubeldia (Spa/Euskaltel) +3:42
11. Denis Menchov (Rus/Rabobank) +3:42
12. Michael Rogers (Aus/T-Mobile) +3:42
13. Eddy Mazzoleni (Ita/T-Mobile) +3:42
44. David Millar (GB/Saulnier) +25:50"
110. Bradley Wiggins (GB/Cofidis) +44:01
1. Oscar Pereiro (Spa/Caisse d'Epargne) 74 hours, 38 mins, 05 secs
2. Carlos Sastre (Spa/Team CSC) +1:50
3. Andreas Kloeden (Ger/T-Mobile) +2:29
4. Cyril Dessel (Fra/AG2R) +2:43
5. Cadel Evans (Aus/Davitamon-Lotto) +2:56
6. Denis Menchov (Rus/Rabobank) +3:58
7. Michael Rogers (Aus/T-Mobile) +6:47
8. Christophe Moreau (Fra/AG2R)) +7:03
9. Levi Leipheimer (USA/Gerolsteiner ) +7:46
10. Haimar Zubeldia (Spa/Euskaltel) +8:06
11. Floyd Landis (USA/Phonak) +8:08
12. Pietro Caucchioli (Ita/C.A) +13:27
59. David Millar (GB/Saulnier) +1 hr 23:44"
130. Bradley Wiggins (GB/Cofidis) +2hrs 34:14"