Rafa Nadal's return to form was stopped in its tracks when he lost his opening match at the Aegon Championships to Ukraine's Alexandr Dolgopolov 6-3, 6-7, 6-4.
The Spaniard arrived in London fresh from winning the Stuttgart Open last week, but his game misfired at crucial moments against the tricky Dolgopolov.
Fifth-seed Nadal, who won the prestigious Queen's Club tournament in 2008 but has stayed away in recent years because of issues with the British tax system, saved a match point in the second set tiebreak and seemed to have taken control in the deciding set when he broke early.
However, Dolgopolov produced a stunning drop volley to break back for 4-4 and crunched consecutive winners, one a searing backhand return and the other a threaded forehand down the line, to seal victory when Nadal served to stay alive.
Earlier, Stanislas Wawrinka needed only 49 minutes to beat Australian Nick Kyrgios as he basked in the glow of his French Open triumph.
The Swiss, who stunned Novak Djokovic to win the title at Roland Garros, picked up where he left off on Paris with a 6-3, 6-4 victory on the sun-drenched west London grasscourts.
Wawrinka, a semi-finalist here last year, will face big-serving South African Kevin Anderson in the next round.
Alexandr Dolgopolov (Ukraine) beat 5-Rafa Nadal (Spain) 6-3 6-7(6) 6-4
Gilles Muller (Luxembourg) beat Mikhail Youzhny (Russia) 6-7(5) 6-4 7-6(5)
Viktor Troicki (Serbia) beat Paul-Henri Mathieu (France) 7-6(4) 1-6 6-4
John Isner (U.S.) beat Jared Donaldson (U.S.) 7-6(11) 6-4
6-Grigor Dimitrov (Bulgaria) beat Sam Querrey (U.S.) 4-6 6-3 6-4
2-Stanislas Wawrinka (Switzerland) beat Nick Kyrgios (Australia) 6-3 6-4
Source: Al Jazeera and agencies