Stefanos Tsitsipas was stunned in the first round of the US Open on Monday after the fourth seed lost to Colombian qualifier Daniel Galan 6-0 6-1 3-6 7-5.
Tsitsipas, 24, was one of five players who could have ended the season's fourth and final Grand Slam as the men's world No 1 but he appeared hampered by an arm injury against Galan, who won the first 11 games and held off an apparent fightback to seal victory on his ninth match point.
Tsitsipas had a physio tend to his right arm before the sixth game in the second set, when he finally got on the board, and again during the break before the third set, when he broke Galan in the second game.
The Greek, who has never got past the third round in New York and had hoped to do better this year after reaching the Cincinnati final, dropped only four of his first-serve points in the third set and looked as though he had the momentum when he broke Galan again in the opening game of the fourth set.
But the Colombian world No 94, playing in the main draw for the first time, never lost his composure, sending across 41 winners throughout the match and refusing to give into his heavily favoured opponent.
"I just stayed calm. I lost the (third) set but I felt I was doing better and better," said Galan.
Dripping with sweat and with the crowd inside Louis Armstrong Stadium egging them on, Galan nearly broke Tsitsipas for the match five times in the 10th game of the fourth set, and finally got the job done in the 12th, gazing at the stands with disbelief.
"I can't explain how I feel right now," he said after the match. "I went through the match well."
Galan next faces Jordan Thompson in the second round after the Australian fought back from two sets down to defeat Italy's Lorenzo Sonego 2-6, 1-6, 6-2, 6-4, 6-4.
There were no such concerns for world No 1 Daniil Medvedev, who began his title defence with a comfortable 6-2, 6-4, 6-0 win over American Stefan Kozlov in sweltering conditions on Arthur Ashe Stadium.
The Russian had an inconsistent run-up to Flushing Meadows but was back to top form on the court where he won his maiden Grand Slam title a year ago, sending across 10 aces and neutralising Kozlov's serve.
"Most pleased to win first of all ... not easy conditions," said Medvedev, who repeatedly wrapped an ice towel around his neck to keep cool in the humid, 85-degree Fahrenheit (29.4 Celsius) conditions. "Serve was quite the key today."
While some struggle with the pressure of being a defending champion, Medvedev is relishing the challenge. The 26-year-old was beaten by Nick Kyrgios in his opening match at the Canadian Masters but reached the Cincinnati semi-final earlier this month.
"I know that I want to play well and if I don't do it, I will not care that I won it last year, I will just be disappointed that this year didn't work out my way," said Medvedev, who faces Frenchman Arthur Rinderknech in the second round.
"I remember last year were some crazy matches. I mean, to be honest, all of them were really high level from me. That's what I want to continue doing this year."
Former champion Andy Murray is also safely through to the second round following his 7-5 6-3 6-3 win over Argentine Francisco Cerundolo, as the former world No 1 rolled back the years at the scene of his first Grand Slam triumph a decade ago.
The 35-year-old Scot, who has battled various injuries in recent years, raced to a 5-2 lead early in the match but dropped his level slightly before edging a tight first set and breaking quickly in the next to put 24th seed Cerundolo under pressure on a sweltering hot Arthur Ashe Stadium court.
"It is obviously nice any time, especially in those conditions and early on in a slam to get through in straight sets," said Murray. "He's a top player, it was a good win for me.
"Mentally it's not easy going into a five-set match in those conditions after the way the last few weeks have been for me, and I did well.
"I did well physically and mentally to put that to the back of my mind and find a way to get through."
The three-time Grand Slam champion takes on American Emilio Nava inn the second round.
Elsewhere in the men's draw, 2020 champion Dominic Thiem's return to the US Open ended in defeat to Spanish 12th seed Pablo Carreno Busta. The Austrian former world No 3, who has been battling a long-term wrist injury and missed last year's title defence, was defeated 7-5, 6-1, 5-7, 6-3.
In the day's final match, Kyrgios defeated close friend and Australian Open doubles title-winning partner Thanasi Kokkinakis in straight sets, the 23rd seed coming through 6-3, 6-4, 7-6.
