Poland's fifth seed Lukasz Kubot was the biggest casualty as the favourites tumbled out on the second day of the Serbia Open in Belgrade.
Kubot was beaten 7-5 6-2 by Lukasz Rosol of the Czech Republic while there were also defeats for sixth seed Fabio Fognini and seventh seed Ryan Harrison.
Italian sixth seed Fognini went down 6-1 6-4 to Frenchman Benoit Paire while American seventh seed Harrison was beaten by Brazilian Joao Souza 6-3 6-3.
Eighth seed Gilles Muller of Luxembourg was Tuesday's only seeded winner with a 6-0 4-6 6-3 win over Slovenia's Lukas Lacko.
Spain's Guillermo Garcia-Lopez was a 7-6 (7-4) 6-7 (7-1) 6-2 winner over Igor Kunitsyn while there were also wins for Romania's Victor Hanescu and qualifiers Antonio Veic, Aljaz Bedene and Eduardo Schwank.