US Open, Flushing Meadows
Dates: 30 August - 12 September Start time: 1600 BST
Coverage: Live text commentary on BBC Sport website and mobiles; updates on BBC Radio 5 live; live on Sky Sports
Roddick was incensed when called for a foot fault in the third set
Ninth seed Andy Roddick saw his hopes of claiming a second US Open title end early with defeat by Janko Tipsarevic in the night session in New York.
The American simply could not contain Tipsarevic's brilliant shot-making as the Serb won 3-6 7-5 6-3 7-6 (7-4).
And Roddick lost his cool with a line judge in the third set as the second-round match began to slip away.
Wimbledon finalist Tomas Berdych was another to suffer a surprise defeat as he lost to France's Michael Llodra.
The seventh seed, who had been a possible quarter-final opponent for Andy Murray, lost 7-6 (7-3) 6-4 6-4 and admitted: "I don't know whether I played well or not, I don't see what I could have done differently.
The on-court temperature topped 100 degrees during Berdych's defeat by Llodra, the world number 35, but the Czech refused to blame his exit on the heat.
In hindsight did I let it go too far? Probably. It was probably a correctable mistake and I let it get to me more than I should have
Andy Roddick on his anger at the line judge
"That had no affect on me at all," he added. "I felt good in the morning and good in the warm-up. Of course, it was hot but that wasn't a problem."
Tipsarevic took control of the night match after dropping the first set and Roddick later admitted that his outburst after being called for a foot-fault had been over the top.
"I wasn't upset with the call, I just expect my umpires to know their left foot from the right foot," said the 28-year-old.
"The stubbornness... I let mine get in the way. I got called for two others after that and have no issue with it. In the moment I was just stupefied.
"It's the fact I couldn't get her to admit it wasn't the right foot which infuriated me, the lack of common sense was unbelievable to me. We have got to be able to have a test like 'Point to your right foot, point to your left foot, now call lines.'
"In hindsight, did I let it go too far? Probably. It was probably a correctable mistake and I let it get to me more than I should have."
Tipsarevic, who was out for three weeks recently with injuries to both ankles, said: "I was playing well, serving well, just had to find my momentum in the right games.
"My first serve percentage really helped me me with my fitness as I was out for three weeks with ankle injuries."
Llodra will play Victor Hanescu in the second round after the unseeded Romanian beat Carlos Berlocq of Argentina 6-2 6-4 6-3.
It was a different story in another shock in the men's draw, as Croatia's 15th seed Ivan Ljubicic admitted he could not come to terms with the conditions during his 6-3 6-7 (4-7) 6-3 6-4 defeat at the hands of US teenage qualifier Ryan Harrison.
"The weather was my biggest enemy today," admitted 31-year-old Ljubicic. "Throughout my career I struggled with the heat. Today was no different.
"I sweat a lot and I just feel really bad. I mean, I can't move. It gets to me really quickly actually. Already in the first set I was struggling with it. It's really a physical problem.
"In Australia they have a pretty good rule. When it's too hot, you just don't play. Hard courts definitely make it worse. The concrete, it's just brutal. You get heat not only from the sky, but also from the bottom."
Elsewhere, Spain's number 14 seed Nicolas Almagro progressed with a 4-6 6-4 6-4 7-6 (7-5) victory over Italy's Potito Starace, while the 25th seed Stanislas Wawrinka of Switzerland thrashed Kazakhstan's Mikhail Kukushkin 6-3 6-2 6-2.
American 20th seed Sam Querrey held off a strong challenge from countryman Bradley Klahn to win 6-3 4-6 7-5 6-4.
France's Gael Monfils, the 17th seed, saw off Igor Andreev 6-3 6-4 6-3, and American 18th seed John Isner defeated Frederico Gil of Portugal 6-4 6-3 6-4.
Isner said afterwards that his ankle felt fine after he turned it in Concinnati two weeks ago, admitting that the Wednesday start had helped him.
"It felt great," he said. "I took a four to six-week injury and got ready in two weeks. I turned it two weeks ago, so it gave me two weeks. It was a lucky break."