Former French Open champion and world number one Gustavo Kuerten looked out of sorts as he was knocked out of the Monte Carlo Masters. The Brazilian, a winner in Monaco in 1999 and 2001, lost 7-6 6-3 to fourth seed Rainer Schuettler of Germany.
Goran Ivanisevic was defeated by French qualifier Nicolas Devilder losing 4-6 6-2 6-2.
There were also defeats for 11th seed Sjeng Schalken, 12th seed Jiri Novak and 13th seed Fernando Gonzalez.
Kuerten struggled on his favourite surface and had to be content with saving a match point before handing victory to his German opponent by floating a return long.
Ivanisevic ran out of steam against Devilder, who is ranked 235th in the ATP entry rankings and was claiming his first ever Masters win.
Of the seeded players who exited, Schalken lost to Agustin Calleri of Argentina 6-1 6-3 while Novak bowed out 6-4 7-5 to American Taylor Dent.
Belarus' Max Mirnyi was too good for Fernando Gonzalez, winning 6-4 6-3 while third seed Guillermo Coria had no problem beating Thomas Enqvist 6-0 6-1.
British number one and sixth seed Tim Henman suffered a scare against American Vince Spadea before coming through 6-7 (5-7) 6-4 7-6 (7-5).