World number one Angelique Kerber was knocked out of the Italian Open in a surprise straight-set defeat by Estonia’s Anett Kontaveit on Wednesday.
The world number 68 won 6-4 6-0 in 56 minutes, meaning both Kerber and men’s top seed Andy Murray exited the Rome tournament at the second-round stage.
British number two Kyle Edmund also suffered a straight-set defeat by Argentina’s Juan Martin del Potro.
The 22-year-old world number 53 lost 7-5 6-4 in one hour and 46 minutes.
Fellow Briton Aljaz Bedene was also knocked out in the second round by world number two Novak Djokovic.
Del Potro, the 2009 US Open champion, will face Japan’s Kei Nishikori in the last 16 as Konta to face Williams in third round
Meanwhile, Rafael Nadal eased through to the third round when opponent Nicolas Almagro retired after injuring his knee early in the first set.
Nadal raced to a 3-0 lead before Spanish compatriot Almagro withdrew with less than half an hour played.
Third seed Stan Wawrinka progressed with a 6-3 1-6 6-3 win over France’s Benoit Paire, with the Swiss facing American John Isner in the next round.
In the women’s draw, American Venus Williams beat Ukraine’s Lesia Tsurenko 6-4 6-3 to set up a third-round meeting with British number one Johanna Konta.
Second seed Karolina Pliskova beat Lauren Davis 6-1 6-1 to progress, while Russia’s Ekaterina Makarova knocked out world number four Dominika Cibulkova 1-6 6-1 6-3.
There were also wins for world number five Simona Halep and eighth seed Elina Svitolina.