World number three Angelique Kerber joined Venus Williams in crashing out of the Western & Southern Open in Cincinnati on Wednesday.
Ekaterina Makarova forced eight match points before finally sealing the deal with a 6-4 1-6 7-6 (13/11) victory over Kerber in a match that lasted more than two and a half hours.
It was a second victory over Kerber this year for Makarova, who also knocked the German out of the French Open in the first round, costing Kerber the number one world ranking.
Williams also suffered disappointment as she was sent home by qualifier Ashleigh Barty, who won 6-3 2-6 6-2 in their second-round clash.
Fourteenth seed Petra Kvitova also crashed out after being beaten 6-2 6-3 by America's Sloane Stephens.
Sixth seed Caroline Wozniacki enjoyed a comfortable 6-2 6-4 win over Elena Vesnina, and number eight Svetlana Kuznetsova beat Yulia Putintseva 6-3 6-4.
Number 11 Dominika Cibulkova saw off Alize Cornet 6-1 6-4 and 15th seed Anastasija Sevastova beat Roberta Vinci 6-2 7-5.
Sixteenth seed Madison Keys beat Daria Kasatkina 6-2 6-1, while qualifier Camila Giorgi beat Daria Gavrilova 7-6 (7/1) 5-7 6-3.
There were also wins for Carla Suarrez Navarro and Julia Goerges in the early session.
Source: PA
