Tenth seed Andy Murray became the first high-profile casualty at the Rome Masters when he lost 6-1, 1-6, 6-3 to France's Gilles Simon in a rain-interrupted first-round match on Monday.
The 19-year-old Briton was one of only two seeds in action on the first day of the claycourt tournament, where the top eight players had all received byes into the second round.
Former French Open champion and 16th seed Juan Carlos Ferrero started slowly, but found his rhythm to beat Dominik Hrbaty of Slovakia 3-6, 6-1, 6-4.
Australia's Lleyton Hewitt also won the first set against Spain's Oscar Hernandez before bowing out 3-6, 7-6, 6-1.
The best-attended match was in the doubles, however, where Roger Federer once again conceded defeat to arch-rival Rafael Nadal, the world number one and his fellow Swiss Stanislas Wawrinka losing 6-4, 7-6 to Nadal and Carlos Moya.
Murray, who broke into the world's top 10 after reaching the semi-finals at the first two Masters Series events of the year in Indian Wells and Miami, was playing his first claycourt singles match of the season after returning from a back injury.
Having dropped his serve three times to lose the first set in just 24 minutes, he rallied impressively to take the second before rain stopped play.
Simon regained his momentum, however, when play resumed over two hours later, using his solid groundstrokes to break an error-prone Murray in his first service game, then summoning up a series of aggressive service returns to go 4-0 ahead.
Murray pulled one break back, but could not prevent Simon closing out the contest.
"I was a bit rusty. I didn't hit the ball well today, and physically I didn't feel great in the long rallies, but generally I thought I did okay," said Murray, who had not lost a first-round match in 2007.
"When you have to take three weeks off and then come out on a surface where you have to play 10 to 12-shot rallies to win points, it's very difficult."