Home favourite Andy Roddick was the major casualty on day three of the US Open at Flushing Meadows.
The ninth seed lost his cool over a foot-fault call as he went down 3-6, 7-5, 6-3, 7-6 to Serbia's Janko Tipsarevic.
Meanwhile, Wimbledon finalist Tomas Berdych crashed out in the first round, losing in straight sets to France's Michael Llodra.
The Czech was thrashed 7-6, 6-4, 6-4 and said after his shock defeat: "I don't know whether I played well or not.
"I had no chance to play on my terms. I don't see what I could have done better or differently."
Fifteenth seed Ivan Ljubicic was knocked out in four sets by 18-year-old American qualifier Ryan Harrison, losing 6-3, 6-7, 6-3, 6-4.