Frenchman Romain Bardet and American Tejay van Garderen's Tour de France podium hopes suffered a major blow overnight when they lost considerable ground in the 16th stage won by Australian Michael Rogers.
Rogers gave his Tinkoff-Saxo team their second stage win this year by powering away from a breakaway group in the 237.5km mountain trek from Carcassonne.
Vincenzo Nibali of Italy retained the overall leader's yellow jersey ahead of Spain's Alejandro Valverde while France's Thibaut Pinot, who was the strongest in the intimidating ascent to the Port de Bales, moved up to third at the expense of compatriot Bardet.
AG2R-La Mondiale rider Bardet, who had promised to blow the race open in the Pyrenees, was unable to sustain the pace in the climb and lost more than 1:40.
Van Garderen also could not follow and lost more than three minutes, but Bardet's team mate Jean-Christophe Peraud could not be shaken off.
''I had good legs, I had to attack,'' Pinot, whose acceleration in the Port de Bales put all his rivals in the red, told reporters.
''I hope I can stay on the podium (all the way to Paris).
The FDJ.fr rider holds the white jersey for the best under-25 rider.
Nibali leads Valverde by 4:37 and Pinot by 5:06 ahead of two tough stages in the Pyrenees.
''This is tough to take in when you were looking to attack,'' said Bardet.
''But there are two stages left in the Pyrenees and I will be looking to attack tomorrow if I have the legs.''
BMC rider Van Garderen now lies 9:25 behind Nibali.
''Movistar made such an insane tempo. I did not have the legs, I felt a bit empty. I'm hoping I can bounce back tomorrow,'' the American said.
World champion Rui Costa of Portugal did not start the stage as he withdrew suffering from pneumonia.
''He was forced to withdraw after an X-ray examination, carried out during the rest day at a clinic in Pezenas, showed an outbreak of pneumonia,'' his Lampre team said in a statement.
A 21-man breakaway took shape after about 60 kilometres and built a 12:30 gap that started to shrink when they hit the first slopes of the ascent to the Port de Bales, a 11.7km climb at an average gradient of 7.7 per cent.
Astana and Movistar set the tempo of the peloton in the climb while Rogers's acceleration in the break reduced the group to seven men.
Thomas Voeckler's attack skimmed it down to four before his Europcar team mate Cyril Gauthier burst away, but he quickly paid for it and was dropped.
Rogers, Colombian Jose Serpa and Voeckler were on their own three kilometres from the summit.
That is where Pinot's team mate Arnold Jeannesson upped the pace in front of the yellow jersey group as Bardet dropped out. Van Garderen was long gone already after Valverde's Movistar team had set a devilish pace at the front.
Pinot finished it off in the last kilometre, dropping Valverde, Peraud and even Nibali.
However, they all came back in the descent and worked together with several team mates who had been dropped from the morning's breakaway and they finished together.
Tomorrow morning's 17th stage is a brutal, 124.5-km effort featuring four demanding climbs with a summit finish at Plat d'Adet.
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