Seeded trio Agnieszka Radwanska, Caroline Wozniacki and Marion Bartoli all crashed to second-round defeats in the Rome Masters.
Third seed Radwanska succumbed to a 6-4 4-6 6-1 loss to Czech Petra Cetkovska while former world number one Wozniacki, seeded sixth in Italy, was forced to retire due to illness after falling 6-4 4-0 behind to Anabel Medina Garrigues.
Wozniacki called for the trainer during the first set of her match in Rome, but she continued to struggle on before deciding she could not continue.
"I have some fever and sore throat, just not feeling great - that makes it even harder to play someone like Anabel on clay," Wozniacki told wtatennis.com.
"I started feeling not great last night. I always get allergies when I come here. It's unfortunate. I'll just try to get some rest now and then get ready for the French Open."
Bartoli was out of sorts against Julia Goerges and the seventh seed fell to a crushing 6-3 6-1 defeat but there was but there was better news for eighth seed and reigning French Open champion Li Na, who dispatched Iveta Benesova 6-1 7-5.
Sam Stosur also made it through despite a spirited second-set fightback from home favourite Sara Errani, the fifth seed claiming a 6-3 7-5 victory.
Twelfth seed Angelique Kerber eased past Vania King 6-3 6-2, while Sorana Cirstea followed up her win over Jelena Jankovic with a comfortable 6-3 6-1 triumph over Sofia Arvidsson.
Top seed Victoria Azarenka beat Shahar Peer, 6-1 6-2, never facing a break point and winning nearly twice as many points in the match.
Serena Williams was made fight to keep alive her hopes of a third successive clay-court title as she came from behind to beat Russia's experienced Nadia Petrova 4-6 6-2 6-3.
Williams, a recent winner in Charleston and Madrid, headed into the match full of confidence but was broken in the first set by the world number 30, who did not allow Williams a glimmer of hope to break back.
But Williams stepped up her game in the second set, breaking Petrova three times again crucially once again in the decider to carve out victory in a match that nudged nine minutes over two hours.
"When I lost the first set, I just thought, 'Stay in there and just don't give up, you'll have a chance,'" said Williams.
"I just didn't want to give up. I never do want to give up, nor have I ever wanted to give up. I wanted it today."
Williams' sister Venus also progressed with a 7-6 (9/7) 6-1 win over Ekaterina Makarova of Russia, while other winners included former world number one Ana Ivanovic.
