Five-time champion Roger Federer defied 32-degree heat and crushing humidity to reach the US Open last 16 as potential semi-final rival Andy Murray almost wilted in the New York sweatshop.
Top seed Federer, bidding to be the first six-time winner in 87 years, defeated Spanish 25th seed Fernando Verdasco 6-3, 6-4, 6-4 in a shade over two hours to make the last 16 for the 12th successive year.
The Swiss next faces American 23rd seed Mardy Fish, who beat Gilles Simon, the French 16th seed, 6-1, 5-7, 7-6 (7/5), 6-3.
Fish prevailed in a match which finished after 0100 local time Sunday morning despite hitting 74 unforced errors.
In stark contrast, third-seeded Murray, the 2008 US Open runner-up to Federer, needed almost four hours to clinch a 7-6 (7/5), 7-6 (7/5), 4-6, 7-6 (7/4) victory over 30th-seeded Spanish left-hander Feliciano Lopez.
Olympic champion Murray will next face 15th-seeded Milos Raonic, who defeated American wildcard James Blake and 6-3, 6-0, 7-6 (7/3) on the back of 29 aces to become the first Canadian to make the last 16 in 24 years.
Murray, four times a Grand Slam runner-up, had lost only one set in six prior matches against Lopez but had to come back from trailing in all three tie-breakers on Saturday.
Federer only faced one break point against Verdasco, a player he has now defeated five times in five meetings.
"I was never really in big trouble on my service games," he said.
"The heat and wind weren't really a problem, but Fernando keeps you guessing, he's a great shot-maker."
Murray's 250th career match victory on hard courts, and his seventh in seven meetings with Lopez, came when the Spaniard netted a backhand.
"This was the first match I had played in this humidity for a while so it was tough," Murray said. "I would like to be in slightly better form but these matches have helped with that."
Eleventh seed Nicolas Almagro kept Spanish hopes alive when he reached the fourth round for the first time with a 7-6 (7/3), 6-7 (4/7), 7-6 (7/2), 6-1 win over American wildcard Jack Sock.
Almagro will meet Czech sixth seed Tomas Berdych, who defeated American 27th seed Sam Querrey 6-7 (6/8), 6-4, 6-3, 6-2.
Croatian 12th seed Marin Cilic, a quarter-finalist in 2009, ended Asian hopes in the singles when he ousted Japanese 17th seed Kei Nishikori 6-3, 6-4, 6-7 (3/7), 6-3.
Cilic will next face unseeded Slovak Martin Klizan who beat doubles partner Jeremy Chardy, the French 32nd seed, 6-4, 6-4, 6-4.
Three-time women's champion Serena Williams went level with sister Venus on 61 US Open career wins when she coasted into the fourth round.
Olympic and Wimbledon champion Williams won eight games in succession to claim a 6-4, 6-0 win over Russia's world 42 Ekaterina Makarova, the woman who knocked her out of the Australian Open this year.
Williams, the fourth seed, fired 31 winners and eight aces and will next face unseeded Czech Andrea Hlavackova, who beat Maria Kirilenko of Russia, the 14th seed, 5-7, 6-4, 6-4.
"After 4-4, I started to play better and more consistent. She's a good opponent, she beat me in Australia so I knew I needed to play better and I did," said Williams, the 1999, 2002 and 2008 champion.
Hlavackova, the world number 82, and making her US Open main draw debut, will be playing in her first Grand Slam fourth round.
Polish second seed and Wimbledon runner-up Agnieszka Radwanska matched her best US Open performance by also reaching the last 16 with a 6-3, 7-5 win over error-plagued Serb 30th seed Jelena Jankovic, the 2008 runner-up.
Radwanska goes on to face Italian 20th seed Roberta Vinci for a place in the quarter-finals.
Vinci reached the last 16 for the first time with a 6-2, 7-5 win over Slovakia's 13th seed Dominika Cibulkova, a quarter-finalist in 2010.
Former world number one and 2008 French Open champion Ana Ivanovic reached the last 16 for the fourth time with a 6-7 (4/7), 6-4, 6-2 win over highly-regarded American teenager Sloane Stephens.
The Serb 12th seed will next face Bulgaria's Tsvetana Pironkova who saw off Spain's Silvia Soler-Espinosa 6-1, 6-7 (3/7), 6-3.
German sixth seed Angelique Kerber, a semi-finalist in 2011, eased past Olga Govortsova of Belarus 6-1, 6-2, and now meets French Open runner-up Sara Errani, the 10th seeded Italian, who defeated Russian qualifier Olga Puchkova 6-1, 6-1.