Astana's Vincenzo Nibali established a commanding advantage in the Tour de France as Belkin rider Lars Boom won the fifth stage in tough conditions.
The Italian finished third behind Boom - who pulled away with six kilometres left - to hold a two-second lead over team-mate Jakob Fuglsang.
Peter Sagan is 44 seconds adrift in third, with Nibali's main rival Alberto Contador 2min 37sec behind the leader.
Reigning champion Chris Froome dropped out after crashing twice.
That leaves two-time winner Contador as Nibali's main rival, but the Spaniard sits 19th in the overall classification after a day that proved difficult for the riders due to the rain and cobbled sections.
Despite organisers taking out two of the nine cobbled sections because of safety concerns - reducing the length of the stage by 2.5km - it was a day of attrition for the riders.
"It was a really stressful day and a very hard race," said Nibali. "I wasn't thinking of the yellow jersey.
"I was just focused on riding the best I could. I'm in good shape. I've prepared for this particular stage but the conditions today were very different from those I experienced when I came and rode on the cobbles."
Froome, who described the conditions as "near impossible", came off twice and abandoned before the cobbles began.
Sagan, Boom and Cancellara were part of a 16-man leading group with 25 kilometres to go, with Nibali - the winner of the second stage - staying with them despite repeated attempts to drop him.
Team Sky's Geraint Thomas and Richie Porte, who is now eighth overall, tried to close the gap, dropping Contador, but eventually finished 21st and 20th respectively.
With 12 kilometres remaining, Boom and Astana's Nibali, Fuglsang and Lieuwe Westra were clear.
Boom built a solid advantage by the time the final cobbled section finished and went on to win by 19 seconds.
The Dutchman said: "I was a special day and a heroic day. With the rain and the cobbles and the mud, it was so nice.
"I saw Astana had a gap so I jumped the gap and we were gone. The guys behind couldn't close the gap and my goal was to drop the guys on the final section."
Stage five result:
1. Lars Boom (Ned/Belkin) 3hrs, 18 mins, 35 secs
2. Jakob Fuglsang (Den/Astana) +19 secs
3. Vincenzo Nibali (Ita/Astana) +19 secs
4. Peter Sagan (Svk/Cannondale) +1 min, 1secs
5. Fabian Cancellara (Swi/Trek) + 1min, 1secs
6. Jens Keukeleire (Bel/Orica GreenEdge) +1min, 1secs
7. Michal Kwiatkowski (Pol/Omega Pharma - Quick-Step) +1min, 7secs
8. Lieuwe Westra (Ned/Astana) +1min, 9secs
9. Matteo Trentin (Ita/Omega Pharma - Quick-Step) +1min, 21secs
10. Cyril Lemoine (Fra/Cofidis) +1min, 45secs
21. Geraint Thomas (GB/Team Sky) +2mins, 19secs
115. Nicolas Roche (Ire/Tinkoff-Saxo) +13mins, 51 secs
140. Simon Yates (GB/Orica GreenEdge) +18mins, 3 secs
1. Vincenzo Nibali (Ita/Astana) 17hrs 07mins 52secs
2. Jakob Fuglsang (Den/Astana) +2secs
3. Peter Sagan (Svk/Cannondale)+44secs
4. Michal Kwiatkowski (Pol/Omega Pharma - Quick-Step) +50secs
5. Fabian Cancellara (Swi/Trek) +1min, 17secs
6. Jurgen van den Broek (Bel/Lotto) +1min, 45secs
7. Tony Gallopin (Fra/Lotto) +1min, 45secs
8. Richie Porte (Aus/Team Sky) +1min, 54secs
9. Andrew Talansky (US/Garmin-Sharp) +2mins, 5secs
10. Alejandro Valverde (Spa/Movistar) +2mins, 11secs
14. Geraint Thomas (GB/Team Sky) +2mins, 16 secs
53. Nicolas Roche (Ire/Tinkoff-Saxo) +13mins, 48 secs
110. Simon Yates (GB/Orica GreenEdge) +26mins, 15secs