Spanish fourth seed Rafael Nadal made it six straight wins over Italian Andreas Seppi, cruising into the third round of the US Open.
World number one and defending champion Novak Djokovic was given a walkover after Jiri Vesely withdrew due to injury. But as the likes of Marin Cilic, Gael Monfils, Jo-Wilfried Tsonga and John Isner won through, Milos Raonic's run came to a halt.
DJOKOVIC TAKES A WALK IN NEW YORK
Djokovic needs no favours to go far in the slams, but he will be more than happy to take the gift of a walkover from Vesely due to inflammation in the Czech's left arm.
The Serbian was scratchy and is battling injuries – to his wrist and arm – of his own, so will undoubtedly be grateful for the rest.
Nadal was in cruise control against Seppi, claiming a 6-0 7-5 6-1 victory in just two hours, 17 minutes.
Cilic, the 2014 champion, disposed Sergiy Stakhovsky 6-1 6-2 6-3, while Monfils, Tsonga and Isner were also barely troubled.
RAONIC, CUEVAS FALL
Canadian fifth seed and Wimbledon runner-up Raonic was stunned, going down to American Ryan Harrison 6-7 (4-7) 7-5 7-5 6-1.
He was the biggest name to fall, but other seeds joined him in exiting at Flushing Meadows.
Pablo Cuevas fell to Nicolas Almagro 7-6 (7-5) 6-4 7-6 (11-9), Benoit Paire suffered a 6-2 6-4 3-6 6-4 defeat to Marcos Baghdatis and Albert Ramos-Vinolas was beaten by Andrey Kuznetsov 7-5 6-4 7-6 (7-5).
UNCHARTERED WATERS FOR EDMUND, ACE ISNER PROGRESSES
Andy Murray is the undoubted king of British tennis, but Kyle Edmund is a man tipped as a future top-10 player and he showed his promise by beating Richard Gasquet in round one.
And Edmund followed up that impressive victory to defeat American wildcard Ernesto Escobedo 7-5 6-4 6-4 to book a spot in the third round of a Grand Slam for the first time.
There was better news for a more established American talent, though, as Isner came through 6-3 6-4 6-7 (10-12) 6-3 against Steve Darcis.
Isner was typically big serving in his victory and he fired down 38 aces and 70 winners.
RAONIC RESPONDS
Raonic battled cramping during his surprise loss, saying: "A little bit of stress. I don't think hydration was an issue. I think I always take that precaution.
"Probably just nerves and stress, a mental sort of over exuberance rather than -- probably more than it should."
Harrison said it had been difficult facing a cramping opponent. "He's a good guy and you don't want him to be seriously hurt," he said. "I wouldn't say I was happy to hear that it was cramping once I heard from the chair that he was getting cramping treatments, but you're certainly happy that it's not like a tear in the hamstring or something like that where he's in jeopardy of being out for a long time."
MURRAY, WAWRINKA RESUME
World number two Murray is expected to have few problems against Marcel Granollers. Stan Wawrinka takes on Italy's Alessandro Giannessi, while Kei Nishikori, Juan Martin del Potro and Nick Kyrgios eye the third round on Thursday.
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