Tokyo: Former champions Kei Nishikori and Tomas Berdych lost at the Japan Open on Wednesday.
Top-seeded Nishikori was forced to retire with a left glute problem in the first set of his second-round match against Joao Sousa.
Third-seeded Berdych fell to Gilles Muller of Luxembourg 7-6 (7), 6-1 in the first round.
Nishikori was 3-0 up when he received medical treatment on his left glute while lying face down on the court for several minutes.
The 2012 and 2014 champ served two weak double faults in the next game, and appeared in pain when chasing the ball. He held serve, but lost the next three games before calling a halt while leading 4-3 in his first matchup with Sousa.
Nishikori, ranked No. 5, saw a doctor after the match, and will have a scan on Thursday.
Sousa moved on to face fifth-seeded David Goffin, after the Belgian beat Jiri Vesely 6-3, 7-5.
Also, fourth-seeded Marin Cilic rallied to defeat Spanish baseliner Fernando Verdasco 4-6, 7-5, 7-5.
Berdych captured his first ATP title of the season when he retained his Shenzhen Open crown in China on Sunday, but his first-round defeat in Tokyo dented his bid for the ATP Finals. He lies ninth in the race for the elite eight-man finals, which he's played for the last six years.
A weary Berdych, the 2008 champ, squandered three break points in the sixth game then failed to convert a set-point in the first tiebreaker.
After falling 3-0 behind in the second set, the Czech called for a trainer to treat a left glute complaint, and was unable to stop Muller, who fired 12 aces.
"At the beginning of the second set, my body gave me a bit of a sign I've been playing a little too much tennis in the last couple of weeks," Berdych said.
Muller, a two-time finalist this year, next faces Marcos Baghdatis.
Berdych and Muller believed Maria Sharapova was lucky to have her two-year doping ban reduced to 15 months.
"Anyone who gives a positive test should get punished. Should they get a reduction? I don't think so, in general," Muller said. "It shows other sportsmen that, at the end of the day, the punishment is not going to be that big."
Berdych said players knew they had to be very careful about any medications.
"Every single time I have to take something, I check many times with many different people," he said.
"At the end, you are the player, you are the athlete, and you are the one who's going to be tested. I always check whatever I take because I'm the one who will go for the (doping) control."
Sharapova received a little more sympathy from Cilic, who has been through the same process as Sharapova. In 2013, he had a nine-month doping ban reduced to four months.
"I was not treated fairly at all," Cilic said. "In my case the system wasn't wrong, the people were wrong. That's behind me. It went to the CAS - it's quite fair whatever they say in most of their decisions. But it's tough to comment on these things because every case is different and individual."