Ivo Karlovic opened up the struggle for the number one ranking as he shocked Roger Federer 7-6 (8-6), 4-6, 7- 6 (7-5) at the Cincinnati Masters to give Rafael Nadal his chance at the top spot, dpa reported.
Federer saved a pair of match points in the third-set tiebreaker but could do little against the 22-ace attack from the 2.08-metre tall Croatian giant, whom he had beaten in all six previous meetings.
It took just over two hours for Federer to fall and leave his top ranking to Nadal, should the Spaniard manage to win the title Sunday at the Ohio event.
Any other scenario would leave the Swiss at the top and facing a huge task at the looming Beijing Olympics.
"When he serves like that, what can you do?" asked Federer, winner of only two minor titles this season and now sporting his most losses (11) since his 17 back in 2003, before his four-and-a-half-year run atop the ATP rankings.
"Maybe if I had won the first set, I'd be sitting here winner in two sets, but it was not to be. It was kind of brutal today."
Federer could not rescue himself despite 48 winners and only 14 unforced errors. It is the only match in his career that he has lost despite never dropping serve.
"I guess I'll analyse and assess my game after the US Open. For the moment it's just all a blur," Federer said.
"It's so many big tournaments in a row. It's hard. It's a tough trip we've got up in front of us now, going back to China and coming back to the Open. But I'm looking forward for the next two tournaments."
Third-seeded Novak Djokovic takes a welcome dose of confidence into Friday's quarter-final with an old foe, after defeating Italy's Andreas Seppi 6-1, 6-2.
The Serb, who holds the Australian Open title, will face former Munich academy schoolmate Ernests Gulbis after the Latvian beat seventh seed James Blake for the second time in two months, 6-4, 1-6, 6-3.
"After the tough two tiebreaks, second-round match (over Simone Bolelli), I managed to really get through with an easy score," said the relived Djokovic, now 42-10 on the season.
Djokovic, 21, has won all three of his matches against Baltic teenaged talent Gulbis, most recently in May in Paris.
Spain's unseeded Carlos Moya completed a match interrupted by rain in the second set Thursday night as he put out Russian fourth seed Nikolay Davydenko 7-6 (10-8), 4-6, 6-2.
On-form Andy Murray beat the heat over Dmitry Tursunov 6-3, 6-3. German Philipp Kohlschreiber out-duelled Swede Robin Soderling 7-6 (7-4), 5-7, 7-6 (10-8).
"They were some of the hottest conditions I've ever played in," said the eighth seed.
"In terms of the match it went pretty smoothly, not too many problems. For me this is tougher than playing in dry heat. The humidity gets to your breathing a little bit and kind of gets you out of breath a lot."