Seeds Fernando Verdasco and Jose Acasuso were the major casualties at the BCR Open in Bucharest on Thursday.
Eighth seed Verdasco of Spain, who beat Tim Henman at the US Open, went down 7-5 7-6 (7-5) to German Florian Mayer.
Spain's Ruben Ramirez-Hidalgo eased past Argentine sixth seed Jose Acasuso 6-4 7-5.
On a good day for Romania, third seed Andrei Pavel beat Oliver Marach 3-6 7-6 (7-2) 6-4, and Victor Hanescu, seeded four, beat Davide Sanguinetti 6-2 6-3.
"It is hard to win in front of your supporters, but I am happy that in the end I gained victory," said Pavel, who goes on to face Mayer.