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.
Roger Federer, who like Murray had a bye into round two, had a much easier time and eased into the third round 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 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.
Spain's world number one Rafael Nadal, who like Murray and the other top seeds had a bye into the second round, will be up against Italy's Andreas Seppi later Wednesday.
World number two Federer clinched the first set with a sweet backhand volley at the net, after stealing the towering Croat Karlovic's serve in the third game.
Another break at the start of the second set was enough for the Swiss, who is looking for his first title of the year, to seal victory.
