Vincenzo Nibali will seek his second major cycling title of the year when the mountain-heavy Spanish Vuelta begins on Saturday.
Joaquim Rodriguez, the other favourite, is hoping to claim a first win at a grand tour to round off a long but incomplete career.
The 68th edition of the race was designed to punish sprinters and indulge climbing specialists with 13 of its 21 stages in the mountains.
The gruelling 3319km race, with two rest days, begins with a team time trial in Rias Baixas on the northwest coast of Galicia and end in Madrid on September 15.
Tour de France winner Christopher Froome, runner-up in the Vuelta in 2011, reigning champion Alberto Contador and Tour runner-up Nairo Quintana are all sitting out the third and final major stage race of the year.
That leaves Nibali, who won the Giro d'Italia in May and the Vuelta in 2010, and Rodriguez as the leading candidates to win the three-week test that will take riders throughout the Iberian peninsula after the 2012 event in northern Spain.
With Movistar's Alejandro Valverde also in the hunt having won the Vuelta in 2009, Rodriguez enters in good form after finishing this year's Tour in third place.
The 34-year-old Catalan has yet to claim a grand tour despite finishing the 2012 season as the top-ranked cyclist. He also was runner-up in the 2012 Giro and third in the Vuelta last year and in 2010.
"I know it's tough to win a grand tour, although I have shown that it's within my reach," Rodriguez said. "Winning one before I retire would be the high point of my career. It's the difference between having a good career, like mine, and a magnificent one."
Following the race's start in the mild weather of the northwest, riders will have to fend off extreme August heat of southern Andalusia before returning to the northern mountains.
The race's single individual time trial comes in the 11th stage. Three days later, riders leave Spain through the Andorran Pyrenees before entering France for a 15th stage that ends in the Peyragudes summit.
Three mountain stages culminate with a summit finish in the Alto de L'Angliru peak on the second last day.
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