Second seed Maria Sharapova was given a tough opening workout in her opening match in Rome on Tuesday.
Sharapova, who impressed on the clay in Stuttgart recently, defeated American Christina McHale in a hard-fought match.
The Russian booked her place in the third round with a 7-5 7-5 victory which took two hours and 12 minutes.
Fourth seed Petra Kvitova also won her second-round match but again was made to fight.
The Wimbledon champion eventually saw off Anastasia Pavlyuchenkova 7-5 6-4.
"I have to say that I was nervous before the match because I saw how she was preparing and I lost my last match against her," the Czech said of Pavlyuchenkova.
"I didn't feel so comfortable, so I'm happy I won, I know where there is space to improve before the next round.
"I'm still learning on this surface. You cannot be two metres behind the baseline. I must move forward and play my aggressive game."
Venus Williams, who required a wild card to make the main draw, won her first-round match against Romania's Simona Halep 6-3 6-4
Serena Williams stretched her winning start to the clay court season to 14 matches as she brushed aside Kazakhstan's world number 46 Galina Voskoboeva 6-2 6-3 in the women's first round.
Williams, who has won successive tournaments in Charleston and Madrid as well as two Fed Cup rubbers since switching from the US hard courts, needed 72 minutes to book her place in round two.
Sorana Cirstea accounted for former world number one Jelena Jankovic 6-3 4-6 7-6 (7/4), while Maria Kirilenko was another seeded casualty, losing 6-1 7-6 (7/2) to Flavia Pennetta.
New Zealand's Marina Erakovic needed two hours and 43 minutes to win a marathon tussle with 11th seed Sabine Lisicki 7-6 (7/4) 4-6 6-3.
Russia's Nadia Petrova was a first round winner over Andrea Hlavackova.
Other winners on a busy day of action were 14th seed Dominika Cibulkova - who eased past veteran qualifier Mirjana Lucic 6-1 6-2 - Karin Knapp, Petra Cetkovska, Sloane Stevens, Flavia Pennetta, Sara Errani and Silvia Soler-Espinosa.