Andy Roddick began his clay-court season with a disappointing three-set defeat by Italian qualifier Flavio Cipolla at the Madrid Open.
The American 12th seed went down 6-4 6-7 (7-9) 6-3 in a match that lasted three hours and two minutes.
Eleventh seed Mardy Fish lost to fellow American John Isner, but Vera Zvonareva and Maria Sharapova won their second-round matches in the women’s event.
“There was a lot of frustration,” Roddick admitted after his defeat.
“It wasn’t a ball-striking thing, it was just a movement thing. The part where I was terrible tonight was moving forward and winning some of those awkward points.
“And once it became a battle of movement his was a lot better than mine on this stuff (clay).”
Fish lost an even closer match 7-6 (7-5) 4-6 7-6 (7-3) to Isner, despite the 6ft 9in big server failing to break serve in the entire match.
Ninth seed Gael Monfils beat Ivo Karlovic 6-3 7-6 (8-6) but fellow Frenchman Richard Gasquet went down 3-6 6-4 6-3 to Daniel Gimeno-Traver of Spain.
World number one Rafael Nadal, who has a bye into round two, will play Marcos Baghdatis after the former Australian Open finalist edged past Colombian qualifier Alejandro Falla 6-3 3-6 7-6 (7-5).
Novak Djokovic, Roger Federer and Andy Murray play their opening singles matches on Wednesday, while the Briton begins his doubles campaign alongside brother Jamie on Tuesday.
Sharapova beat fellow Russian Ekaterina Makarova 6-3 3-6 6-1 to reach round three, and insisted afterwards that her ambitions go beyond her recent return to the world’s top 10.
“Everyone has the goal of being number one,” said the 24-year-old, who has battled with a serious shoulder injury in recent years.
“It’s a great achievement for me to get back into the top 10 but that’s not where I want to end. I see myself going a lot further than that.”
Second seed Zvonareva recovered from losing the first six games to beat Elena Vesnina 0-6 6-3 6-3 and there were wins for French Open champion Francesca Schiavone, former world number one Dinara Safina and Australian Open finalist Li Na.
However, defending champion Aravane Rezai slumped to a 6-3 3-6 6-4 defeat by Swedish qualifier Sofia Arvidsson.