Serbian top seed Ana Ivanovic crashed out of the Italian Open in her first match on Wednesday, losing 6-4 5-7 6-2 to Bulgarian qualifier Tsvetana Pironkova.
Russian world number two Maria Sharapova survived a scare to beat unseeded Slovak Dominika Cibulkova 6-2 3-6 6-4, but the other leading seeds including title holder Jelena Jankovic and the Williams sisters had less trouble in the second round.
Ivanovic made an untidy start with too many groundstrokes finding the net or going long and she soon went down a break, but she broke back in the ninth game only to fail to hold immediately after and concede the set.
The world number three twice surrendered a break advantage in the second set and let a string chances to take the Bulgarian's serve again go begging before she finally managed to level things up.
But the unforced errors kept flowing and she was broken three times on the way to losing the decider.
"I felt quite flat out there and I found it a struggle to find my rhythm and find something inside to fight," Ivanovic told a news conference.
"I really struggled with my intensity today and obviously that caused a lot of errors. It's something I have to work on. Now I have 10 days to prepare for the French Open."
After an early trade of breaks, Sharapova took the upper hand against Cibulkova with some big hitting, although she needed seven set points on her serve to take the first set.
The Slovakian was not deterred and, after another exchange of breaks in the middle of the second set, she pinched Sharapova's serve with a nice drop shot before serving out to level the score.
The Russian then edged a topsy-turvy final set of seven breaks to creep home.
Seventh seed Venus Williams, returning from more than a month on the sidelines with an unspecified medical problem, beat Australian Samantha Stosur 6-4 6-1 while her fifth-seeded sister Serena crushed Ukrainian Alona Bondarenko 6-2 6-0.
Jankovic, the fourth seed, progressed in straight sets too with a 6-1 6-4 victory over Italy's Flavia Pennetta.
Russian third seed Svetlana Kuznetsova, the woman Jankovic defeated in last year's final, had an easy 6-2 6-0 win over Belarusian Olga Govortsova.