British number two Cameron Norrie was knocked out of the Delray Beach Open in Florida by teenager Brandon Nakashima, who is ranked 294th in the world.
Norrie, 24, who has a world ranking of 60, lost 7-5 6-2 to the 18-year-old American in the second round.
Nakashima, who is competing in his debut ATP Tour event on a wildcard, is the youngest player in the tournament.
On Tuesday, British number three Kyle Edmund was forced to withdraw because of illness.