Fourth seed Agnieszka Radwanska became the first major casualty of the US Open when she was dumped out in the second round by Peng Shuai.
Radwanska dropped just one game in a rapid first-round win over Sharon Fichman but world number 39 Peng was a deserved 6-3 6-4 winner.
The Chinese player looked like she might have missed her chance when two match points went begging, one on the Radwanska serve at 5-3 and the second on her own delivery.
Radwanska had a chance to make it 5-5 but missed it and Peng took her third match point with a backhand winner onto the line.
It was deja vu for Radwanska, who suffered her only previous loss to Peng in the second round at Flushing Meadows four years ago.
Radwanska came into the tournament in a positive frame of mind after winning the title in Montreal earlier this month but she has never found the US Open a happy destination.
The Pole has reached at least the quarter-finals at every other grand slam but has not made it past the fourth round here.
Radwanska said: “It always is disappointing (to go out), especially in the first week of a grand slam. But I think here it’s not really a new thing for me unfortunately.
“I really want to know the answer. Then maybe I will find a way to play better here and just try another way to be in the second week.
“There is just something here that I can’t really pass those rounds. I have couple of years to try. Hopefully one day I will do it.”
Radwanska did not feel she gave a bad performance, saying: “Every game was pretty tight and a lot of rallies. But I think in the important moments she was just playing a little bit better.”
There was disappointment, too, for 21st seed Sloane Stephens, who from a set and 3-0 up against Johanna Larsson slumped to a 5-7 6-4 6-2 loss.
The American had balanced out poor performances in regular tour events with success at the slams but lost in the first round at Wimbledon and has underachieved again here.
There was a notable victory, meanwhile, for 17-year-old Belinda Bencic, who defeated 31st seed Kurumi Nara 6-4 4-6 6-1.