Two-time French Open finalist Dominic Thiem was stunned by veteran Spaniard Pablo Andujar in the first round at Roland Garros.
Thiem has struggled for form since winning his first grand slam title at the US Open last summer but looked to be finding a way past Andujar when he opened up a two-set lead.
However Andujar, who beat Roger Federer in Geneva last week, fought back to win 4-6 5-7 6-3 6-4 6-4 and record his first victory over a top-five player at the age of 35.
Thiem took a six-week break in March and April to step back from the demands of the tour and bubble life and must now reflect on a first opening-round loss at Roland Garros.
The 27-year-old, who was seeded fourth, has reached at least the quarter-finals on his previous five visits, losing to Rafael Nadal in the final in 2018 and 2019.
Elsewhere, there were wins for Roberto Bautista Agut, Pablo Carreno Busta, Karen Khachanov and Fabio Fognini.
Sixth seed Alexander Zverev rallied from two sets down to beat qualifier Oscar Otte 3-6 3-6 6-2 6-2 6-0 in his opening round.
The 24-year-old seemed to be heading for an early exit like Thiem, who beat him in the 2020 US Open final, when he lost the first two sets on the Suzanne Lenglen Court but he found a different gear to turn around the contest.
For the rest of the match, it was one-way traffic against the 152nd-ranked Otte in the first meeting between the two Germans as Zverev's movement on the red clay improved and he found more power in his shots and more sting in his serves.
Greek Stefanos Tsitsipas overcame a sluggish start to reach the second round with a 7-6(6) 6-3 6-1 victory over France's Jeremy Chardy.
The fifth seed, who extended his winning run on clay to five matches after clinching the title in Lyon last week, was in trouble in the opening set in an empty court Philippe Chatrier after spectators were sent home under a 9 pm local time curfew before making his superiority count.
Tsitsipas, who lost to 13-times Roland Garros champion Rafael Nadal in the final in Barcelona, steamrolled past a helpless Chardy in the other two sets.
He ended Chardy's challenge after just over two hours with a forehand winner for a no-nonsense victory.
He will next face either American Sebastian Korda or Spain's Pedro Martinez.