Andrey Rublev's Monte Carlo Masters title defence ended at the first hurdle on Wednesday with a straight-sets defeat by Australian Alexei Popyrin, while Jannik Sinner eased through.
The Russian never got going in the second-round tie as Popyrin eased to a 6-4, 6-4 win at the traditional clay court warm-up for the French Open.
The world number 46 will face compatriot Alex de Minaur, who beat Tallon Griekspoor in three sets, for a possible quarter-final against Novak Djokovic.
"I enjoyed coming out on centre court for the first time. First tournament on clay of the year and I have good memories from clay last year," said Popyrin, who won his second ATP title in Croatia on clay in 2023.
"I am feeling really comfortable on it and happy to beat a guy who was in form, confident and the defending champ. It was an awesome match."
The loss extended a poor run of form for Rublev, after a defeat in his opening match against Tomas Machac in Miami and losing to Jiri Lehecka in the Indian Wells last 32.
The sixth seed had a break point to level at 5-5 in the second set, but found the net and Popyrin closed out the victory.
Rublev lifted his first Masters 1000 title in Monaco last year by beating Holger Rune in the final.
Australian Open champion Sinner cruised through, though, seeing off American Sebastian Korda 6-1, 6-2.
The world number two converted seven of the 12 break points he created and saved all three of the ones he faced in a dominant performance.
The Italian will next play Jan-Lennard Struff of Germany in the last 16.
"Every year, it's tough to come here and try to perform well, but I'm very happy about this performance and let's see what is coming in the next round," said Sinner, who lost to Rune in the semi-finals 12 months ago.
"I haven't served very well, but I returned very well, I stayed close to the baseline."
Angry Medvedev through
Daniil Medvedev made short work of a potentially tricky opening tie with Gael Monfils, sealing a 6-2, 6-4 win.
But it was not all plain sailing for the Russian on court as he remonstrated with umpire Mohamed Lahyani over a line-judge call.
Trailing 4-1 in the second set, Medvedev recovered his composure to win five straight games and open his clay court season with an authoritative win.
"It was a tactical game here and there but I felt good," said Medvedev.
"I played good speed where I could defend well and not give him (Monfils) two easy balls."
The world number four will next go head-to-head with fellow Russian Karen Khachanov in the third round, with either Alexander Zverev or Stefanos Tsitsipas waiting in the last eight.
Speaking about his next opponent, the 2021 US Open champion said: "I think Karen likes (clay) more but I can play well on clay... Even when I am 45 I can say I have a Rome Masters title, so I can play well on it and I am happy about it."
Medvedev has reached at least the semi-finals in all four of his previous tournaments so far this season.
Two-time champion Tsitsipas showed signs of a return to his best, thrashing Argentina's Tomas Martin Etcheverry 6-1, 6-0 in just over an hour.
French 14th seed Ugo Humbert progressed with a 6-1, 6-4 success against China's Zhang Zhizhen.
He will next take on Lorenzo Sonego, who ensured former top-10 player Felix Auger-Aliassime's miserable run of form continued, winning 6-4, 7-5.
Italy's Sonego only reached the main draw as a lucky loser after the withdrawal of Carlos Alcaraz.
Poland's Hubert Hurkacz also went through in straight sets, defeating Roberto Bautista Agut 7-5, 7-6 (7/4).
Three-time Grand Slam runner-up Casper Ruud is up next for Hurkacz, after the Norwegian brushed aside Alejandro Tabilo 6-2, 6-4.
Rain then swept in during the early evening, forcing the suspension of play with seventh- and ninth-seeds Rune and Grigor Dimitrov both one set to the good respectively.
Play will resume Thursday with Denmark's Rune up a set and a break against Indian Sumit Nagal and Miami Open finalist Dimitrov leading Serb Miomir Kecmanovic.
