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Sixth seed Alexandr Dolgopolov suffered a shock 6-3 6-3 loss to Ivan Dodig in the first round of the Delray Beach International Tennis Championships.
The Ukrainian was broken four times by his Croatian opponent, who is ranked 40 places below him, as he slumped to defeat in just under an hour.
There were no such problems for the other two seeds in action - Sam Querrey and Xavier Malisse.
Third seed Querrey progressed from his all-American clash with Michael Russell when his opponent withdrew with an apparent injury. Querrey was leading 6-2 2-2 at the time.
"I thought that was the best attitude I've had all year. It's the most aggressive I've been all year," Querrey said.
"I was hitting second serve returns and taking cracks at them, and dominating with my forehand. It felt great."
Malisse of Belgium saw off Alejandro Falla of Colombia 6-3 6-3, but his compatriot Steve Darcis was ousted 7-6 (7-5) 6-3 by Russia's Evgeny Donskoy, who will face Dodig next.