World number one Roger Federer and number two Rafael Nadal pulled out of the Hamburg Masters due to fatigue, organisers said on Monday.
Nadal, 19, beat the Swiss in Sunday's Rome Masters final in a match that lasted more than five hours to equal Guillermo Vilas's record of 53 straight wins on clay.
The Spaniard will have to wait until the French Open, which begins at the end of the month, to make the 29-year-old mark his own.
Only five of the world's top 10 now remain in the tournament's weakest line-up in years. Argentina's David Nalbandian, American Andy Roddick and Australia's Lleyton Hewitt had already withdrawn.
Last year's winner Federer and Nadal will travel to Hamburg for medical check-ups as tour rules dictate and will be replaced in the draw by Sweden's Robin Soederling and Lukas Dlouhy of the Czech Republic.
Croatia's Ivan Ljubicic, number five in the world, is now the highest ranked player in the tournament followed by Nikolay Davydenko of Russia, the world number six.
In the day's first-round matches, Brazilian qualifier Flavio Saretta stunned 2000 Hamburg finalist Marat Safin 5-7, 6-0, 6-4, while American fifth seed James Blake scored a fine 6-3, 3-6, 7-5 win against former French Open champion Carlos Moya.
Moya's Spanish compatriot and former Roland Garros champion Juan Carlos Ferrero defeated Belgian Olivier Rochus 7-6, 5-7, 6-3 while another Spaniard, eighth seed Tommy Robredo, beat Jiri Novak of the Czech Republic 6-3, 6-2.
French teenager Richard Gasquet lost 6-4, 6-2 to Kristof Vliegen of Belgium and another Spaniard, Fernando Verdasco, knocked out Argentina's Juan Ignacio Chela 1-6, 6-4, 6-2.
