Top-seeded John Isner lost to qualifier and fellow American Ryan Harrison in the second round Wednesday at the Sydney International tennis event, a final Australian Open tune-up.
Harrison took down his taller compatriot by a 6-4, 6-4 margin at Sydney Olympic Park Tennis Centre.
The 6-foot-9 Isner is battling a sore right knee and is questionable for the Aussie Open, which gets underway Monday in Melbourne.
"I got a decision to make shortly," he said. "It was a lot better than it was six days ago, but it wasn't 100 percent. What I have needs time, that's all it is."
Meanwhile, Denis Istomin, Bernard Tomic and last year's Sydney runner-up Julien Benneteau also pulled off upsets. Uzbekistan's Istomin beat fourth- seeded Spaniard Fernando Verdasco 6-3, 6-3, the Aussie crowd favorite Tomic defeated fifth-seeded German Florian Mayer 7-6 (7-4), 6-2 and the French Benneteau moved on when sixth-seeded Czech Radek Stepanek retired from their match in the first game due a back injury.
Italian Andreas Seppi, the No. 3 seed, outlasted wild card John Millman of Australia by a 6-2, 3-6, 6-3 margin, while eighth-seeded Spaniard Marcel Granollers beat Fabio Fognini of Italy 6-2, 7-6 (7-4).
Reigning Sydney champion and 2009 runner-up Jarkko Nieminen of Finland cruised past Ivo Klec of Slovakia 6-3, 6-1, while South Africa's Kevin Anderson defeated Feliciano Lopez of Spain 6-3, 6-4. Klec replaced No. 2 seed Gilles Simon of France in the draw. The 2011 Sydney champion Simon pulled out due to neck injury.
Thursday's quarterfinals will pit Seppi against Granollers, Tomic versus Nieminen, Harrison against Benneteau, and Istomin versus Anderson. Nieminen beat Benneteau in last year's finale here.