WIMBLEDON, England (AP) — The recurring cries of “Come on, Andy!” at Centre Court meandered somewhere along the continuum from pushing to pleading as two-time champion Andy Murray’s shortest stay at Wimbledon came to a close.

Unable to overcome big John Isner’s big serves, the way he always has in the past, the revered Murray lost in the second round to the 20th-seeded American 6-4, 7-6 (4), 6-7 (3), 6-4 on Wednesday night at the All England Club, capping a disappointing afternoon and evening in the grass-court Grand Slam tournament’s main stadium for the locals.

Prior to Murray vs. Isner, the host country’s other leading player, reigning U.S. Open champion Emma Raducanu, was eliminated by Caroline Garcia of France 6-3, 6-3.

Asked whether he plans to be back a year from now, the 35-year-old Murray replied: “It depends on how I am physically. If physically I feel good, we’ll try to keep playing. But it’s extremely difficult, with the problems I’ve had with my body the last few years, to make predictions.”

Murray needed multiple operations on his hip and now has an artificial joint. He also recently dealt with an abdominal issue that hampered his preparations last week.

In addition to becoming Britain’s first men’s singles title winner in 77 years at Wimbledon when he claimed the trophy in 2013 — and adding another in 2016 — Murray always had managed to make it to at least the third round in his 13 prior appearances. He lost that early twice, in his 2005 debut and in 2021.

“It’s no secret that I am most definitely not a better tennis player than Andy Murray. I might have been just a little bit better than him today. It was an incredible honor to play him on this court, in front of this crowd,” said the 37-year-old Isner, who won the longest match in tennis history by a 70-68 score in the fifth set at Wimbledon in 2010 and reached the semifinals there in 2018. “At the age I’m at now, I need to relish these moments. This was one of the biggest wins of my career.”

Murray can still hit crisp, clean groundstrokes, and he accumulated merely 13 unforced errors to 39 winners against the 6-foot-10 (2.08-meter) Isner. And Murray can still return about as well as anyone, often getting serves topping 130 mph (210 kph) back over the net. But he could not quite do that enough: Isner hit 36 aces — moving him four away from Ivo Karlovic’s total of 13,728, a record since the ATP began tracking that stat in 1991 — and delivered another 60 unreturned serves across the match’s nearly 3 1/2 hours.

Murray, who entered the day 8-0 against Isner, only managed to obtain two break points. Both came after about a dozen minutes of play, right after Isner broke to go up 2-1 in the opening set.

Isner erased the first with a drop volley winner, part of a tremendous display of deft touch up at the net, where he won the point on 43 of 61 trips forward.

“This is why I still play,” Isner said. “This is why I work hard.”

When the second break chance for Murray arrived moments later, Isner got out of the game this way: 128 mph (206 kph) ace, 126 mph (203 kph) ace, 134 mph (216 kph) service winner.

Murray made things interesting by taking the third-set tiebreaker, celebrating by hopping around and shouting and pumping his right fist while the crowd rose and roared.

But Isner quickly broke to go up 3-2 in the fourth and that, essentially, was that.

How did Isner hold off any chance of a comeback by Murray?

“I served,” Isner said with a laugh. “That’s really all it came down to. I guess I didn’t give him many opportunities to spin his web and get me tangled up in it. If I got embroiled in too many rallies with him, it just wasn’t going to go well for me. I had an incredible serving day and I needed every single bit of it to beat him.”

Next for Isner is a third-round matchup against No. 10 seed Jannik Sinner. Other men who won Wednesday included three-time defending champion Novak Djokovic and No. 5 Carlos Alcaraz, while No. 3 Casper Ruud — the runner-up to Rafael Nadal at the French Open — lost 3-6, 6-2, 7-5, 6-4 to Ugo Humbert, and No. 15 Reilly Opelka was defeated by Tim Van Rijthoven 6-4, 6-7 (8), 7-6 (7), 7-6 (4).

Only four of the top 11 men in the ATP rankings are in the bracket after Day 3.

In addition to No. 10 Raducanu’s exit, No. 2 Anett Kontaveit lost to Juke Niemeier of Germany 6-4, 6-0, and No. 9 Garbiñe Muguruza, the champion at Wimbledon in 2017 and the French Open in 2016, was beaten by Greet Minnen 6-4, 6-0.

Women’s winners included 2021 runner-up Karolina Pliskova, No. 8 Jessica Pegula, three-time major champion Angelique Kerber and 2017 French Open champion Jelena Ostapenko.

Raducanu won the championship at Flushing Meadows in September as an unseeded player who went through qualifying at age 18.

Since then, she’s had a birthday — and has not made it past the second round at a major.

“There’s no pressure. Like, why is there any pressure? I’m still 19. Like, it’s a joke. I literally won a Slam,” Raducanu said. “Yes, I have had attention. But I’m a Slam champion, so no one’s going to take that away from me. Yeah, if anything, the pressure is on those who haven’t done that.”

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