World number three Juan Carlos Ferrero gave up his Monte Carlo Masters title, slumping out in the first round 6-2 6-3 to fellow Spaniard Alex Corretja. The holder was continually out-rallied by his opponent, a former world number two now ranked 100th.
Lleyton Hewitt fared better, battling back to beat Julien Benneteau 3-6 6-3 6-4 to record his first event win.
Marat Safin, runner-up at Estoril on Sunday, also staged a comeback to beat Belgium's Olivier Rochus 4-6 6-3 6-3.
Spanish fifth seed Carlos Moya edged past Sargis Sargsian 7-6 (7/5) 1-6 6-3.
Seventh seed David Nalbandian beat Dominik Hrbaty 6-3 6-0 after seven weeks out, while ninth seed Nicolas Massu beat Flavio Saretta 6-3 6-0.
Eighth seed Sebastien Grosjean cruised through with a 6-4 6-2 victory over fellow Frenchman Arnaud Clement.
But 10th seed Paradorn Srichaphan was beaten 6-4 6-3 by Juan Ignacio Chela.
 | My main goal is the French Open. I know I can play well on clay  |
Hewitt was a first-round loser to Carlos Moya in his only other Monte Carlo appearance in 2002.
The Australian struggled with his serve and made 32 errors against Benneteau.
But he came through to set up a meeting with Argentine Gaston Gaudio, who beat Italy's Filippo Volandri 4-6 7-5 6-4.
"I got better as the match went on," said Hewitt.
"I didn't have my footing at the start and was maybe being a bit too aggressive.
"My main goal is the French Open. I know I can play well on clay. It's about confidence and getting some rhythm."