Rafael Nadal made an early exit at Queen’s Club with a three-set defeat by unseeded Ukrainian Alexandr Dolgopolov.
The Spanish fifth seed led by a break in the final set but went down 6-3 6-7 (6-8) 6-4 in round one of the Aegon Championships.
Nadal, 29, had arrived in London following victory at the Stuttgart grass-court event on Sunday.
French Open champion Stan Wawrinka and title holder Grigor Dimitrov both progressed.
Wawrinka began his grass-court season with a 6-3 6-4 win over Australia’s Nick Kyrgios, and Dimitrov completed a 4-6 6-3 6-4 victory over Sam Querrey.
Britain’s Andy Murray beat Taiwanese qualifier Yen-Hsun Lu, before US Open champion and fourth seed Marin Cilic beat Frenchman Adrian Mannarino 7-6 (7/3), 3-6, 6-2.
Dolgopolov sees off Nadal
Nadal made a slow start against Dolgopolov, dropping serve immediately and almost falling a double break behind.
Dolgopolov served out the first set with little fuss, keeping Nadal at bay with his unorthodox mix of pace and spin, and had his first chance to win the match at 6-5 in the tie-break in the second set.
A swinging serve saved Nadal and the 2008 champion seemingly made the decisive move early in the third, converting his first break point after one hour and 42 minutes.
However, a time violation followed for the Spaniard and Dolgopolov got back on level terms at 4-4, fending off three break points before grabbing his second match point with a forehand winner.
“I was fighting in every point,” Nadal said. “I was with the right concentration, with the right motivation, not giving up when I had tough moments.
“I’m not happy I lost a match that I had a chance to win, but that’s it. That’s tennis on grass.”
‘Sick’ Kyrgios struggles
Second seed Wawrinka had earlier impressed in his first match since winning at Roland Garros, needing just 49 minutes to see off Kyrgios, last year’s Wimbledon quarter-finalist.
“I’m happy with the way I’m playing already,” he told BBC Sport.
The Swiss goes on to face big-serving South African Kevin Anderson in the second round of the Wimbledon warm-up event.
Kyrgios said afterwards that he had been “sick for the last week”, adding: “I just felt uncomfortable the whole time.
“He hit the ball massive, free swinging out there. I almost found it difficult to get myself engaged and didn’t want to be there.”
Wawrinka responded: “It doesn’t really surprise me. When I read his interviews, it’s always funny, a lot of things you can take.
“When I read before the match, he was ready, excited for the challenge, and now he is sick.
“So I’m just saying he’s saying a lot of things, and I think it’s always interesting as a player to read what he’s saying and how his mind is working.”
Dimitrov had been in trouble against Querrey on Monday, with the American leading by a set and a break before being pegged back.
It was the Bulgarian who pushed hardest on Tuesday’s resumption, earning three break points before finally converting a fourth with a rasping forehand winner at 4-4.
“I was very positive and woke up in a good spirit,” said the sixth seed.
Berdych through in Halle
Third seed Tomas Berdych reached the second round of the Gerry Weber Open in Halle, Germany, beating Victor Estrela Burgos 7-5 6-3.
Second seed Kei Nishikori also progressed, as did Bernard Tomic and Gael Monfuls, with Roger Federer having won on Monday.