Stan Wawrinka was beaten 6-4 6-4 in the first round of the Italian Open on his return from injury.
The Swiss three-time Grand Slam champion lost to 55th-ranked American Steve Johnson on the clay in Rome.
The 33-year-old sat out the second half of 2017 after knee surgery following his first-round exit at Wimbledon and has not competed since February.
"I really only started to play tennis again 12 days ago," said Wawrinka, who hit 30 unforced errors to Johnson's 17.
He returned at the start of the year but retired during a second-round match in Marseille in February, against then world number 193 Ilya Ivashka of Belarus, and has not competed since.
"I think when I came back in Australia [in January] it was quite clear I wasn't ready at all," said Wawrinka, who spent eight weeks on crutches following the surgery.
"But for me it's important to play matches to test myself playing against the top guys.
"I'm happy with physically where I am right now.
"I had a lot of hesitation with my game and it obviously makes a big difference in the way I move and the way I play."
"It's positive to see that the knee was doing okay, but now I need a lot of time to work on my fitness. Today was tough but I'm really happy to see where I am right now.
"I'm close to my top level, I still need a lot of time to play matches."
Three Americans advanced on the first day on the red clay in Rome with 13th seed Jack Sock beating Spaniard David Ferrer 6-3, 6-4, and Ryan Harrison ousting Japan's Yuichi Sugita 7-6 (7/5), 6-3.
But 12th-seeded American Sam Querrey fell 6-2, 7-6 (9/7) to Germany's Peter Gojowczyk while Italian wild card Lorenzo Sonego came back from a set down to defeat France's Adrian Mannarino 2-6, 7-6 (7/4), 6-4.
Seven-time Rome winner Rafael Nadal is the top men's seed as the world number one competes after suffering his first clay-court defeat in almost a year in the Madrid quarter-finals to Austrian Dominic Thiem.
This defeat saw him handing back the number one ranking to Switzerland's Roger Federer, at least for this week. If Nadal wins in Rome, however, he could reclaim the top spot.
In the ATP Race, Nadal is third, while Roger Federer is first.