Former champion Andy Schleck of Luxembourg has pulled out of the Tour de France following a crash in the third stage.
His team Trek said: "We are sad to announce that Andy Schleck cannot take the start ... today.
"The ligaments and meniscus in the right knee are too severely damaged from his crash in yesterday's final.
"He will travel to Basel now for examination and a possible operation."
Schleck won the 2010 Tour after Spain's Alberto Contdor was stripped of the title for doping.
However, he has been struggling since sustaining a hip injury the 2012 Criterium du Dauphine.
He said in a team statement: "This is a huge blow for me. I went on the rollers as soon as we arrived in Le Touquet, to get the muscles and tendons warmed up, but the pain is too much.
"I believed until that moment that I would start. I think I ignored the pain somehow, hiding it in the back of my head.
"I'm hugely disappointed. I was so happy to be here, racing with Frank (his brother) in the Tour again.
"I'm sad to let the team down, to let Frank down. I was ready to help him defend his GC ambitions. I felt I was progressing, everything was coming back."
Meanwhile, defending champion Chris Froome crashed as the race resumed in northern France.
The Team Sky leader suffered a grazed left hip and torn cycling shorts after a touch of wheels in the peloton on the 163.5km stage from Le Touquet-Paris-Plage to Lille.
He began the day in fifth overall after the first three stages in England.
Froome was swiftly back on his bike after the collision, which also brought down Bauke Mollema (Belkin), and rejoined the main pack.
His wrist appeared to be the main concern and team-mate Vasili Kiryienka was given a splint from the team car for Froome's use.
Race doctor Florence Pommerie told France Televisions: "They're essentially a few scratches, but that's got to hurt nevertheless.
"He also hurt his wrist, but we'll have to wait and see how it goes."
The Briton had been hoping for an incident-free day ahead of Wednesday's cobbled route from Ypres to Arenberg Porte du Hainaut, which could shake up the general classification.