Ricardo Mello of Brazil upset last year's finalist John Isner of the United States 6-4, 7-6 (4) on Tuesday in the first round of the Serbia Open, while former fifth-ranked Fernando Gonzalez of Chile made a winning return from an eight-month injury layoff.
The big-serving Isner had 18 aces but Mello converted the only break point of the first set to take control of the match. The Brazilian then saved four of the five break points he faced in the second before prevailing in the tiebreaker.
Gonzalez beat qualifier Martin Klizan of Slovakia 6-2, 6-4 after recovering from hip surgery. The 30-year-old Gonzalez dominated the first set, although both players struggled to hold serve in the second. Klizan double-faulted on Gonzalez's second match point.
Gonzalez will next play Feliciano Lopez of Spain who upset eighth-seeded Argentine Juan Monaco 6-4, 7-5.
Lopez made the decisive break in the 11th game of the second set on a wind-swept day at the ATP tour event organized by the family of Novak Djokovic.
"To beat Monaco on clay, you have to be confident," Lopez said.
Sixth-seeded Ernests Gulbis also went out, losing 6-2, 6-4 to Illya Marchenko of Ukraine.
The 108th-ranked Ukrainian, who converted four of five break points, next faces Filippo Volandri of Italy who beat Serbian wild card entrant Dusan Lajovic 6-1, 6-4.
India's Somdev Devvarman rallied to beat Mikhail Kukushkin of Kazakhstan 1-6, 6-4, 6-2 and qualifier Adrian Ungur of Romania defeated Ruben Ramirez Hidalgo of Spain 6-7 (2), 6-3, 6-4.
Ungur will next play the second-ranked Djokovic, who is opening his clay court season on Wednesday after winning 24 consecutive matches this year, including victories at the Australian Open and hard-court tournaments in Dubai, Indian Wells and Miami.
Michael Berrer of Germany beat Alexander Peya of Austria 4-6, 6-3, 6-4 and Marcel Granollers of Spain defeated Franco Skugor of Croatia, 7-5, 6-1.