Andy Murray's Rome Masters campaign floundered at the first hurdle when he lost 1-6, 6-3, 7-5 to Argentine qualifier Juan Monaco on Wednesday, but Rafael Nadal and Roger Federer enjoyed comfortable wins.
Spain's world number one Nadal, who like Murray and the other top seeds had a bye into round two, beat Italy's Andreas Seppi 6-2, 6-3, while Federer progressed with a 6-4, 6-4 win over Ivo Karlovic.
British fourth seed Murray looked in total control as he fired some cracking winners from deep when running away with the opening set.
But Monaco, who put up a good fight against the Scot in Miami last month, took advantage of some sloppy shots to roar back.
The 21-year-old Murray twice broke back in the second set of a match postponed on Tuesday due to rain but he could not recover after losing his serve again in its eighth game.
It was almost an identical story in the deciding set, with Murray slicing the ball into the net to concede the match and allow the Argentine to set up a third-round clash with 15th seed Marin Cilic.
The Rome crowd briefly had hope of seeing their man spring another surprise when Seppi took Nadal's serve in the first game with a big forehand return.
But the Spaniard hit back with three breaks of his own in the first set and another in the second to march on to an encounter with Swede Robin Soderling.
World number two Federer clinched the first set of his match with a sweet backhand volley at the net, after stealing the towering Croat Karlovic's big serve in the third game.
Another break at the start of the second set was enough to seal victory for the Swiss, who is looking for his first title of the year and will now meet Radek Stepanek, the Czech who knocked him out in the quarter-finals here last year.
"I got off to a good start in both sets, which is always kind of comforting against Ivo," Federer told a news conference.
"He found his groove on his serve later but I already had the break in the second, which is perfect.
!It was important to be really solid on my serve. I had two close service games in the beginning. From then on, I was pretty much cruising."
Murray was not the only top 10 seed to fall on Wednesday. Nikolay Davydenko (seventh) lost 7-5, 7-6 to Austria's Juergen Melzer and France's Jo-Wilfried Tsonga (ninth) went down 7-6, 6-4 to his compatriot Richard Gasquet.
