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Only one British player remains in the Wimbledon singles draws after Johanna Konta was knocked out on day four.
Elsewhere, world number ones Rafael Nadal and Simona Halep were in action, three-time champion Novak Djokovic had an injury scare, the seeded players continued to fall, and Nick Kyrgios had another run in with the authorities.
Here are five things from Wimbledon.
After just four days of the championships, six of the top 10 women's seeds and four of the top 10 men have already exited SW19.
Marin Cilic is the latest name in the men's draw to bow out - and arguably the biggest shock, given that he reached the final last year and beat Novak Djokovic at Queen's in the build-up to Wimbledon.
The Croatian third seed led Guido Pella by two sets when play was called off on Wednesday, but Pella produced a remarkable comeback on Thursday to stun Cilic 3-6 1-6 6-4 7-6 (7-4) 7-5.
The drama continued into the late evening when defending women's champion and third seed Garbine Muguruza was toppled by Belgian Alison van Uytvanck.
Muguruza, a two-time Grand Slam champion who dominated Venus Williams in last year's final, fell to a 5-7 6-2 6-1 loss.
She is the first women's defending champion to lose inside the first two rounds at Wimbledon since Steffi Graf fell in the first round in 1994.
Three-time Grand Slam champion Stan Wawrinka also exited on Thursday when his rain-affected match resumed.
Wawrinka was down two sets when play resumed against Italian Thomas Fabbiano but, unlike Pella, he was unable to turn the scoreline in his favour.
Denis Shapovalov, the 26th seed, and 27th seed Damir Dzumhur also saw their Wimbledon journeys come to an end in the second round.
Twelve British players started the tournament in the men's and women's singles draws but only Kyle Edmund remains.
Wild card Katie Boulter was knocked out early on Thursday before British number one Johanna Konta suffered an early exit, losing to Dominika Cibulkova, much to the disappointment of the Centre Court crowd.
Konta, who will now will now drop out of the world's top 40, was dominated in the match, saying afterwards her opponent played "incredibly well".
But after Konta's defeat Kyle Edmund turned the disappointment into exuberant celebration when he beat Bradley Klahn to reach the Wimbledon third round for the first time.
It was also 23-year-old's first victory on Centre Court and the Yorkshireman punched the air wildly after winning match point.
"You grow up watching Wimbledon and dreaming of playing here so to get my first win here will always be memorable," Edmund said.
He will play three-time champion Djokovic next...
Djokovic has dropped to 21st in the world rankings after injury troubles this season
Djokovic reached the third round with a routine win over Argentine Horacio Zeballos but late in the third set the Serb called for the trainer for treatment on a muscle injury in his left leg.
In the closing stages the 12-time Grand Slam champion winced when putting pressure on his leg but afterwards said the issue was "nothing major".
"Tomorrow I'll see on the practice session how it feels," he added. "Hopefully it's going to be fine.
"It's most likely a twitch, you know, in the muscle or something like this that has affected the knee a little bit.
"I've been doing check-ups now, it seems like nothing major."
Another of the favourites for the title, Spaniard Rafael Nadal, progressed in straight sets against Mikhail Kukushkin but was challenged at times in an entertaining match.
The former champion was given a time violation during the match for taking too long to change his clothes and after the match said he should have gone "to the toilet" to avoid the issue.
Australia's Nick Kyrgios, a controversial but entertaining character, was in impressive form en route to victory over Robin Haase.
But he was involved in two exchanges with the umpire, one after receiving a code violation for inappropriate language and later after a foot fault.
Kyrgios questioned the call from the line judge, asking "What, after I hit it? How's that possible?", to which umpire James Keothavong said: "That's what he has to do. He can't call it before you hit it."
Even Kyrgios was amused by that. The umpire later came down from his chair to demonstrate the rule as Kyrgios watched on.
The 23-year-old was then asked about the exchanges in his post-match press conference...
You seemed to get upset about the code violation.
NK: Not upset at all.
You spoke to the umpire while the Mexican wave was going on for quite some time.
NK: Does that make me upset?
You had a word with the line judge, as well.
NK: Does that make me upset?
Were you upset?
NK: No.
Why did you have a word with the line judge?
NK: Because you generally, like, talk to someone when you're curious about something. Doesn't make you upset, champ. Good question.
Ninth seed Isner was taken to five sets by Ruben Bemelmans but saved two match points to win.
The 6ft 10in American hit 64 aces in the match - the third most in a match at Wimbledon, only bettered by the 113 and 110 managed by Isner and Nicolas Mahut when they played the longest match in Wimbledon history in 2010.
