Venus Williams withdrew from the US Open, saying she is battling debilitating Sjogren's Syndrome but hopes to return to tennis soon.
Williams, winner of back-to-back titles at Flushing Meadows in 2000 and 2001, had been scheduled to take on Germany's Wimbledon semi-finalist Sabine Lisicki, the 22nd seed, in a second round match.
Williams was unseeded at the US Open for the first time since her debut in 1997 - when she made it to the final.
She was playing in just her fourth tournament of 2011 thanks to injury and illness.
Since a first-round defeat at Wimbledon, she had withdrawn from WTA events at Toronto and Cincinnati with what was called at the time a viral illness.
After her 6-4, 6-3 first-round victory over Russian Vesna Dolonts on Monday, Williams said her illness had sapped her energy but declined to go into details.
On Wednesday she was more specific.
"I'm really disappointed to have to withdraw from this year's US Open," she said in a statement. "I have been recently diagnosed with Sjogren's Syndrome, an auto-immune disease which is an ongoing medical condition that affects my energy and causes fatigue and joint pain."
After her first round victory, Williams had been upbeat about the odds that she would be fit enough to go as far as her game would take her in a Grand Slam.
"I think I'll be OK," Williams said, but she spoke too soon.
"I enjoyed playing my first match here and wish I could continue, but right now I am unable to," she said Wednesday.
"I am thankful I finally have a diagnosis and am now focused on getting better and returning to the court soon."