Britain's Johanna Konta let two match points and a commanding lead slip as she lost to Russia's Ekaterina Makarova at the Rogers Cup in Toronto.
Makarova won 5-7 7-6 (7-4) 6-3 and will face Lucie Safarova in round three.
Konta, who had a first-round bye as the seventh seed, was playing her first match since losing to Venus Williams in the Wimbledon semi-finals.
The Briton, 26, led 7-5 5-2 but failed to convert two match points in the second set.
Makarova, 29, is ranked 42nd but extended her winning streak to seven matches after claiming the Washington title last week.