Defending champion Jurgen Melzer crashed out of the ATP and WTA US National Indoor Championships on Tuesday, losing his opening-round match in straight sets.
The left-handed Austrian lost to Dutchman Igor Sijsling 6-4, 7-6 (7/3) at The Racquet Club of Memphis.
Sijsling advanced to a second-round match against Croatian top seed Marin Cilic.
Melzer, who was playing with a broken toe, defeated Milos Raonic in last year's final, snapping the Canadian's win streak at nine straight matches.
American veteran James Blake defeated German Florian Mayer 4-6, 6-3, 6-2. Blake, who got into this year's tournament as a wild card, was runner-up in this event 11 years ago.
In other men's matches, US lucky loser Michael Russell beat Russian qualifier Alex Bogomolov 6-2, 6-4.
On the women's side, Slovakian seventh seed Magdalena Rybarkova reached the third round by ousting American Lauren Davis 7-6 (7/2), 6-2.
France's Claire Feuerstein upset Czech fifth seed Lucie Hradecka 6-3, 6-4 while German third seed Sabine Lisicki reached the second round with a 7-5, 6-3 victory over American Madison Keys.