Nadal, 25, was talking to journalists, two hours after his third round win over close friend David Nalbandian, when he grimaced in pain, screwed up his eyes and slumped in the back of his chair, feeling his right leg.
The world number two, a winner of 10 Grand Slam titles, slipped to the floor while tournament medical staff were summoned.
Scores of reporters and camera crews were ushered out of the packed interview room deep inside the Arthur Ashe Stadium.
However, after 15 minutes of treatment, Nadal was back on his feet, insisting that the problem was merely cramping.
"It was just cramping in the right leg, in the front and in the back. It was very painful, that's all," said Nadal, who resumed his news conference standing instead of sitting.
A smiling Nadal said the incident will not affect his preparations for his fourth round match against Luxembourg's Gilles Muller, scheduled for Tuesday.
"I will train normally on Monday. It was just a normal cramp that could have happened anywhere, but it's just bad luck that it happened in the press room. Anywhere else, nobody would have noticed."
During his 7-6 (7/5), 6-1, 7-5 win over Nalbandian, played out over 2hr 39mins in heavy, 84 degree-heat (29 degrees centigrade), Nadal also needed treatment on his blistered right foot.
Muller, who reached the last 16 by beating Russia's Igor Kunitsyn 6-1, 6-4, 6-4, famously defeated Nadal at Wimbledon in 2005 before the Spaniard got his All England Club revenge this year.
British fourth seed Andy Murray, the 2008 runner-up, took his career record against Spanish left-hander Feliciano Lopez to six wins in six meetings thanks to an impressive 6-1, 6-4, 6-2 victory over the 25th seed.
Murray, who had to come back from two sets down to defeat Dutchman Robin Haase in the second round, didn't concede a point on his own serve in a brutal first set on Sunday which set the tone for the one-sided tie.
He now faces American wildcard Donald Young, the former world junior number one, who reached the fourth round at a Grand Slam for the first time with a 7-5, 6-4, 6-3 win over Argentine 24th seed Juan Ignacio Chela.
Argentine 18th seed Juan Martin del Potro, the 2009 champion, who missed last year's title defence because of a serious wrist injury, saw his hopes dashed by Gilles Simon in a four-hour marathon.
The French 12th seed booked his place in the last 16 for the first time with a 4-6, 7-6 (7/5), 6-2, 7-6 (7/3) win over del Potro who committed 72 unforced errors and squandered three set points in the 10th game of the fourth set.
Simon will face 28th seed John Isner who defeated fellow American Alex Bogomolov 7-6 (11/9), 6-4, 6-4.
Spanish fifth seed David Ferrer, a semi-finalist in 2007, beat German 26th seed Florian Mayer 6-1, 6-2, 7-6 (7/2) and next tackles 2003 winner Andy Roddick.
The American 21st seed breezed past French wildcard Julien Benneteau 6-1, 6-4, 7-6 (7/5) and then laughed off the incident involving Nadal.
"When you go to bed and your foot cramps, it's the same thing but your entire leg," said Roddick, who said he wasn't surprised that Nadal had ended on the floor.
"That's just a matter of what part of your body cramps. Cramp in your ass, you can't sit on it anymore. Makes it tough."
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