The top two seeds at the German Tennis Championships each made early exits on Tuesday, together with home favourite Tommy Haas.
Albert Ramos-Vinolas - the highest-ranked player in the field - lost a deciding-set tie-break to lucky loser Leonardo Mayer in Hamburg, while last year's runner-up, Pablo Cuevas, was edged out 3-6 7-5 6-4 by Andrey Kuznetsov.
Uruguay's Cuevas has now suffered two defeats in as many matches since returning from a knee injury.
Haas lost in straight sets to Argentina's Nicolas Kicker, 20 years on from making his debut at the tournament.
There were also wins in round one of the ATP 500 clay-court event for Federico Delbonis, Philipp Kohlschreiber and Karen Khachanov.
Jiri Vesely and Fernando Verdasco will resume their contest on Wednesday having shared the first two sets.
Dusan Lajovic was the only seed to fall in the Swiss Open Gstaad, going down in straight sets to Dustin Brown.
There were no such problems for Robin Haase and Joao Sousa, who each progressed comfortably. Radu Albot and Thiago Monteiro were the other opening-round winners on Tuesday.