Defending champions Rafael Nadal and Maria Sharapova both crashed out on a day of shocks at the BNP Paribas Open in Indian Wells.
Sharapova was upset 6-3 4-6 7-5 by Italian qualifier Camila Giorgi while Nadal fell 6-3 3-6 7-6 (7/5) to Ukrainian Alexandr Dolgopolov.
The world number one had struggled past Radek Stepanek in his first match and was a long way from his best against in-form 28th seed Dolgopolov.
He looked to have saved the day when he first recovered from a set down and then broke his opponent when he served for the match at 5-3 in the deciding set.
Nadal led 4-2 in the tie-break but simply could not find his range and Dolgopolov took his first match point despite seeing what he thought was an ace overturned by HawkEye.
The Ukrainian powered away a forehand instead to set up a fourth-round meeting with Italian Fabio Fognini, who saved two match points on his way to victory over Gael Monfils.
Nadal admitted after beating Stepanek that the back injury that hampered him in the Australian Open final had taken away his confidence on serve, but speaking after losing to Dolgopolov, he said: "I played bad. That's all.
"I'm disappointed with the way I played. But that happens sometimes. I did all that I had to do to be in good shape.
"I worked very hard for the last week. After Rio I had a few days off to recover the back. Then I think I worked great, and with good feeling. But since I started the competition here I didn't find the right feelings.
"I saved a tough situation the first day. Today I was close to saving another one. But at the end, when you are on the limit, these things happen.
"You can lose. I lost today. I congratulate him. He played I think better than me. That's it. Life continues. I'm going to keep working hard to try to be ready for Miami."
Dolgopolov put together a video earlier this month featuring the likes of Nadal, Novak Djokovic and Andy Murray wishing for peace in Ukraine.
He said: "It's a moment for the people to be proud a little bit for someone from their country, I guess.
"It's good to make some results and make the people forget a little bit and have some happy moments in the news except the politics and all the bad stuff happening."
Sharapova is still finding her feet after missing the last three months of last season with a shoulder problem but had looked in decent form in her first-round win over Julia Goerges.
She was wobbly right from the start on Monday, though, against powerful and fearless 22-year-old Giorgi, who reached the fourth round at the US Open last summer.
Sharapova failed to hold serve at all in the first set at Indian Wells Tennis Garden and there were 15 breaks in total.
Giorgi faltered serving for the match for the first time but Sharapova gave her another chance and this time she took it.
The Russian will drop to at least seventh in the rankings, and she said: "I did not play a good match at all, and I started very poorly.
"I'd never played against her, but she's someone that doesn't give you much rhythm. She's quite aggressive, but some shots she hits incredibly for a long period of time. Sometimes they go off a bit.
"But if I'm speaking about my level, it was nowhere near where it should have been.
"I think the physical part of it is something that is hurting me a little bit when we're going into these three-set matches. That's not a secret for anyone.
"And when you skip those months there's nothing that gets back that match play than just going out and doing it."
Roger Federer avoided the shocks but had to battle his way through two tie-breaks to beat Russian Dmitry Tursunov 7-6 (9/7) 7-6 (7/2).
Federer's Swiss compatriot Stanislas Wawrinka does not appear to have had any kind of comedown after winning the Australian Open and was ruthless in beating Andreas Seppi 6-0 6-2.
Women's top seed Li Na was a relatively comfortable 6-3 6-4 winner over Czech Karolina Pliskova and will play Canada's Aleksandra Wozniak, who upset 21st seed Anastasia Pavlyuchenkova 6-1 6-7 (3/7) 6-0.
There were also victories for Petra Kvitova, Australian Open runner-up Dominika Cibulkova and American Sloane Stephens, who knocked out Ana Ivanovic.