Former world number one Serena Williams has withdrawn with a toe injury in Cincinnati, disrupting her preparations for the US Open later this month.
The American has won two titles this summer after a year out with injury and illness, but pulled out ahead of Wednesday's match against Sam Stosur.
Williams had beaten Stosur to win the Rogers Cup in Toronto on Sunday.
World number one Caroline Wozniacki suffered a shock defeat in Cincinnati, losing to US wildcard Christina McHale.
The American, ranked 76th, held her nerve to see out a 6-4 7-5 victory that leaves Wozniacki desperately short of form ahead of the US Open later this month.
The Dane , where she was defending champion.
"I can't remember the last time I had two first-round exits," she said. "It's a bit different. You know, I usually play better as the week goes on, but what happens, happens."
With the US Open starting on 29 August, both Wozniacki and Williams have under two weeks to get into shape for the final Grand Slam tournament of the year.
Williams, who cut her foot on some glass at a restaurant last year and needed two operations, said: "I don't think this is a good time for me to take a big chance. I just don't think that would be smart.
"It's not as bad as it was before. It's just a lot of match play. I've been playing a lot of the matches, more than I have in a long time, and also training as well. It got a little aggravated. Instead of making it worse, I've decided it will be in my best health not to go on."
In other matches, Italian seventh seed Francesca Schiavone beat Maria Kirilenko 7-5 3-6 6-4, and Russian 14th seed Svetlana Kuznetsova beat Petra Cetkovska 4-6 6-3 6-4.
Unseeded Russian Nadia Petrova defeated 15th seed Ana Ivanovic 6-3 7-6 (7-4), and there was another blow to the tournament when third seed Victoria Azarenka withdrew ahead of the night match with a right hand injury.
"It's impossible to play for me," said the Belarussian. "I was waiting until the last moment to be 100% sure that I cannot compete.
"It's important also prior to the US Open. It just doesn't make any sense to make it worse."