Briton Chris Froome's hopes of winning the Vuelta a Espana look to be over after he finished Wednesday's stage more than seven minutes behind the general classification leader.
Froome had been hoping to become the third man to win the Tour de France and Vuelta a Espana in the same year but he crashed early on stage 11.
It was won by Spain's Mikel Landa from the Astana Pro Team.
Italian team-mate Fabio Aru took the overall classification lead.
"It was a real demonstration of strength and I'm really happy to be in the leader's jersey," said Aru.
"There's still 10 stages to go and so we'll take things day by day but we'll try to defend it."
Dutchman Tom Dumoulin had been in the red jersey at the start of the day but he finished almost three minutes back at the end of a punishing mountain stage.
Spaniard Landa had surged clear of a splintered field around nine kilometres from the steep finish into Cortals d'Encamp, while team-mate Aru came second and Froome's Team Sky team-mate Ian Boswell third.
Froome limped home almost nine minutes behind the stage winner and afterwards team-mate Geraint Thomas said that the Tour de France winner had injured a foot, knee and shoulder.
Team Sky later tweeted that the team leader had gone to hospital for an X-ray on his foot after struggling to put weight on it.
The 30-year-old had started the day in eighth place, one minute, 18 seconds off the lead, he is now seven minutes 30 seconds behind the leader with his victory hopes in tatters.
Wednesday's eventful stage also included more motorbike controversy.
Tinkoff Saxo rider Sergio Paulinho had to withdraw from the race after colliding with a television motorcycle, an incident that left the Portuguese racer taken to hospital needing 17 stitches on a leg injury.
It is the second time in four stages that a Tinkoff Saxo rider has been hit by a motorcycle after Peter Sagan was hit in the eighth stage and had to withdraw.
After that crash, the team asked race organiser Unipublic for a public apology and a sum "equal to the value of the prize" for a stage victory to be paid to a charity of Tinkoff and Sagan's choice.
After Tuesday's rest day, Wednesday's 11th stage was a mountainous 138km race from Andorra la Vella to Cortals d'Encamp. The 12th stage on Thursday is a 173km flat race from Escaldes-Engordany to Lleida.
The 21-stage Grand Tour finishes in Madrid on 13 September.
Froome not the only big name to struggle
BBC Sport's Matt Slater: "When you are trying to do something that only the greats have done, it is a good idea not to do something that usually only happens to dozy amateurs: crashing into a barrier, five minutes into the ride, whilst going uphill.
"Froome answered every question about his bike-handling and racing skills at the Tour de France, only to fluff an easy one he did not see coming on Wednesday.
"To his credit, he fought on, limiting his losses on the final climb of a brutal day at the Vuelta.
"He was not the only big name to struggle, though, with his great adversary at the Tour, Nairo Quintana, also looking tired, leaving the way clear for the more rested Fabio Aru to take charge.
"And Froome's crash was arguably not even the most sensational. That dubious honour went to Sergio Paulinho, the second Tinkoff-Saxo rider to be wiped out by a motorbike in this race. The row about that one could be seismic."
Stage 11 result:
1. Mikel Landa (Spa/Astana) 4hrs 34mins 54secs
2. Fabio Aru (Ita/Astana) +1min 22secs
3. Ian Boswell (US/Team Sky) +1min 40secs
4. Daniel Moreno (Spa/Katusha) +1min 57secs
5. Joaquim Rodriguez (Spa/Katusha) +1min 59secs
6. Rafal Majka (Pol/Tinkoff - Saxo) +2mins 10secs
7. Mikel Nieve (Spa/Team Sky) same time
8. Esteban Chaves (Col/Orica) +2mins 59secs
9. Tom Dumoulin (Ned/Giant) same time
10. Diego Rosa (Ita/Astana) +3mins 02secs
32. Chris Froome (GB/Team Sky) +8mins 41secs
52. Nicolas Roche (Ire/Team Sky) +14mins 25secs
53. Geraint Thomas (GB/Team Sky) +14mins 51secs
82. Stephen Cummings (GB/MTN - Qhubeka) +24mins 34secs
1. Fabio Aru (Ita/Astana) 43hrs 12mins 19secs
2. Joaquim Rodriguez (Spa/Katusha) +27secs
3. Tom Dumoulin (Ned/Giant) +30secs
4. Rafal Majka (Pol/Tinkoff - Saxo) +1min 28secs
5. Esteban Chaves (Col/Orica) +1min 29secs
6. Alejandro Valverde (Spa/Movistar) +1min 52secs
7. Daniel Moreno (Spa/Katusha) +1min 54secs
8. Mikel Nieve (Spa/Team Sky) +1min 58secs
15. Chris Froome (GB/Team Sky) +7mins 30secs
22. Nicolas Roche (Ire/Team Sky) +13mins 03secs