Former champion Andy Roddick has been bundled out of the US Open in the second round after he lost to Serb Janko Tipsarevic in four sets.
The 2002 Open winner cruised through the opening set in just 40 minutes but struggled afterwards as Tipsarevic produced a memorable display to win 3-6 7-5 6-3 7-6 (7-4).
With the match played at night, the oppressive heat that haunted many players on day three was less harsh but Roddick was unable to contain Tipsarevic's brilliant shot-making - he hit 66 winners compared to Roddick's 40.
Tipsarevic hit 16 aces compared to the American's 17 as Roddick lost his cool with a line judge deep in the third set.
Roddick delivered a verbal spray to the official and may be fined for his conduct.
Earlier in the day, No.4 seed Andy Murray cruised into the second round with a straight-sets victory over Slovakian Lukas Lacko.
Murray began his campaign for a first Grand Slam title with a comfortable 6-3 6-2 6-2 victory, crushing Lacko in one hour and 51 minutes.
The Briton will face Jamaican Dustin Brown in the second round.
Other upsets included Frenchman Michael Llodra defeating Wimbledon finalist and No.7 seed Tomas Berdych, and 18-year-old qualifier Ryan Harrison easing past No.15 seed Ivan Ljubicic.
Berdych was unable to find an answer for Llodra's powerful serve, going down 7-6 (7-3) 6-4 6-4.
Llodra moves into the second round where he will face Romanian Victor Hanescu.
US teenager Harrison delighted the home crowd with a 6-3 6-7 (4-7) 6-3 6-4 victory over an out-of-sorts Ljubicic.
The Croatian made an astonishing 51 unforced errors to hand the match to his inexperienced opponent, who faces Ukrainian Sergiy Stakhovsky in the second round.
Sam Querrey overcame a stern test from fellow American Bradley Klahn, dropping the second set before prevailing 6-3 4-6 7-5 6-4 against the No. 596-ranked wildcard.
France's Gael Monfils and American John Isner were both straight-sets winners over Igor Andreev and Frederico Gil respectively.