Ailing Novak Djokovic suffered his earliest Grand Slam exit in 20 years on Sunday, falling in five brutal sets to Mariano Navone in the first round of the US Open.
The 48th-ranked Argentine's 7-6 (7/5), 5-7, 4-6, 6-2, 6-1 victory ended Djokovic's latest bid for a record 25th Grand Slam title, the monumental achievement looking ever less likely for the 39-year-old.
It also ended his run of 78 Grand Slam first-round victories, a streak stretching all the way back to Djokovic's 2006 loss to Paul Goldstein at the 2006 Australian Open.
"I think it was obvious that it was an awful feeling on the court for me," said Djokovic, who vomited several times and battled late-match cramps.
"It's something that I've been carrying, unfortunately, pretty much every match this year. Vomiting, throwing up, a serious issue there. Then my whole body starts to collapse, basically cramping and pain.
"The back just gave up in the end and shoulder, I couldn't close it out."
Djokovic, who took medication during the match, appeared to have finally taken control when he broke Navone for a 2-1 lead in the fourth set with a vintage backhand winner down the line.
But Navone won the next five games, raising his arms in celebration after fighting off two break points for a 5-2 lead and breaking Djokovic again to force the fifth.
Djokovic took a medical timeout before the final set, receiving massage on his spine and more medication.
But Navone jumped to a 3-0 lead in the decisive set and despite the urging of fans there was no road back for the Serb as his opponent dropped just one point on his own serve as he sprinted to the finish line.
Djokovic, a four-time US Open champion, had never lost before the third round in Flushing Meadows, but he'd shown signs of frailty in his only tune-up, struggling physically in losing his opening match in Cincinnati.
Even as he grabbed a 4-1 lead in the first set Djokovic was clearly not himself. Every rally left him gasping, and he finally surrendered the set with a dismal forehand into the net.
In a tense second set Djokovic missed break chances in the third and fifth games before breaking Navone at love for a 6-5 lead and holding at love to level the match at one set apiece.
The third set was more of the same, Djokovic seizing the crucial break in the ninth game and fending off a break point in the next for a two sets to one lead.
That put paid to any thought he'd had of retiring.
"I have, I have," he said when asked if he'd thought of throwing in the towel. "But then I won a set and then the third. I didn't want to give up."
Determination wasn't enough. He was 2-1 up in the fourth set when the cramps struck and lost eight games in a row.