Former champion Lleyton Hewitt's time at the US Open has come to an end at the racquet of fellow Australian Bernard Tomic in New York.
But in a typically battling effort from Hewitt - who won the US Open back in 2001, as well as Wimbledon the following season - the 34-year-old came back from two sets down to force a fifth set, before losing the decider 7-5.
Hewitt even had a match point in the ninth game, serving at 5-3.
But it wasn't to be, Tomic recovering to win their second round clash 6-3 6-2 3-6 5-7 7-5 and finish the veteran's career at the New York grand slam.
Hewitt's retiring after next January's Australian Open. Tomic goes on to face French 12th seed Richard Gasquet.
Day four saw extremely humid conditions with a record 12 players in the men's draw retiring.
Fourth seed Caroline Wozniacki was the day's biggest upset, the Dane losing to 30-year-old Petra Cetkovska.
The Czech Republic veteran won the first set but then had to fight off four match points to win in a third-set tiebreak, Cetkovska triumphing 6-4 5-7 7-6.
She next plays Italian 26th seed Flavia Pennetta.
Also progressing to the third round were two other Czechs, fifth seed Petra Kvitova and sixth seed Tomas Berdych, as well as second seeds Roger Federer and Simona Halep, and third seed Andy Murray.
Contrasting outings for Murray, Federer
Murray needed five sets on centre court to see off France's Adrian Mannarino, who was the losing Auckland finalist in January.
Mannarino took the first two sets but wilted in the heat as the Scot found his game to win 5-7 4-6 6-1 6-3 6-1 and book a third round clash with Brazilian Tomaz Bellucci.
Also on Arthur Ashe Stadium, Federer had no problems with Belgian journeyman Steve Darcis, winning 6-1 6-2 6-1 to reach the third round, where the Swiss great will face 29th-seeded German Phillipp Kohlschreiber.
Federer took just 80 minutes to register victory over the 66th-ranked Darcis. He's lost just nine games in his first two matches at Flushing Meadows this week.
The 34-year-old's now matched American great Serena Williams for most US Open wins under the lights as he improved his record to 29-1.
"I've enjoyed myself so many times, so many years. It's wonderful that I can still experience it and play this well. It's great," Federer said in an on-court interview. "I hope this is not my last one, of course."
Mixed fortunes for Kiwi doubles players
New Zealand Davis Cup player Marcus Daniell won his doubles debut at the US Open on Thursday.
The Wairarapa native teamed up with Jonathan Marray, a Wimbledon winner two years ago, to win in three sets against American wildcards Reily Opelka and Taylor Harry Fritz.
Daniell and Marray took the match 6-3 4-6 6-3.
Another New Zealander, Artem Sitak, bowed out in his first round doubles match with Israeli partner Jonathan Erlich, in a close encounter decided by a couple of close shots in the final tiebreak.
Italian pair Andreas Seppi and Marco Cecchinato took the match 6-7 6-3 7-6.
"It was just a couple of points here and there and we probably didn't take our opportunities when we should of. It's a tough loss, but it's so tight out there and so close," said Sitak, who is ranked 45 in the world.
Sitak's alive in the mixed doubles though, with Ukrainian partner Elina Svitolina - they take on Australian Nick Kyrgios and Canadian Eugenie Bouchard.
Also on Saturday, compatriot Michael Venus and Croatian doubles partner Mate Pavic face the 12th seeds from France, Pierr-Hughes Herbert and Nicolas Mahut, in their second round match.