Two-time champion Alberto Contador has joined defending champion Chris Froome in abandoning the 2014 Tour de France.
Contador crashed on the 161.5-kilometre 10th stage from Mulhouse to La Plance des Belles Filles and, after struggling on in an effort to play catch-up, he gave up and withdrew to his Tinkoff-Saxo team car.
The Spaniard's departure deprives the race of another previous winner after 2013 champion Froome withdrew with fractures to his left wrist and right hand on stage five last Wednesday.
The action on the Bastille Day stage was expected to ignite on the concluding climb ahead of Tuesday's rest day, but the Tour lost another leading protagonist after Mark Cavendish's crash on day one and Froome's exit.
Contador crashed on the approach to the third of six categorised climbs, the Col du Platzerwasel.
The Spaniard received strapping to his right knee and lost four minutes as a result of the delay, falling nine minutes behind the day's breakaway, which held a five-minute lead on the peloton.
The Astana team of Vincenzo Nibali led the main bunch and did not increase the pace on the 7.1km, category one ascent as Contador's team-mates dropped back to help him.
Contador began the day in ninth place, four minutes and eight seconds behind Frenchman Tony Gallopin (Lotto-Belisol), who seized the race leader's yellow jersey from Nibali.
But the Spaniard struggled to reduce the arrears in the mist-shrouded Vosges Mountains with more than 80km of the stage remaining.
The finish at La Planche des Belles Filles was a reminder to Britons of the absent Froome and Sir Bradley Wiggins.
Froome won at the summit of the 'climb of the beautiful girls' in 2012 as Wiggins took the yellow jersey he held until Paris, when he became the first British winner of the race.
Contador's withdrawal could see him refocus on the Vuelta a Espana, which begins in Jerez on August 23. The race could yet also feature both Froome and Wiggins.
At the front of the race the breakaway riders were hunting King of the Mountain points, with Joaquim Rodriguez (Katusha) cresting the summit of the Col du Platzerwasel first, Thomas Voeckler (Europcar) conceding defeat in the chase and going over in second place.
The pair had been joined in the escape by Peter Sagan (Cannondale), but he dropped back on the third ascent after winning the day's intermediate sprint to increase his stranglehold on the points classification's green jersey.
Michal Kwiatkowski (Omega Pharma-QuickStep) was the highest-placed of the escapees at the start of the day and had Sunday's stage winner Tony Martin for support.
Ted King (Cannondale) began the day in 183rd and last place, but abandoned after struggling early on the 10th stage.