Simona Halep suffered a worrying leg injury just over two weeks out from the French Open at the Internazionali BNL d'Italia, where Serena Williams and Naomi Osaka crashed out.
Halep, the 2018 French Open champion, had dominated the first set against Angelique Kerber, winning 6-1, but came off the court with an apparent calf problem with the scores level at 3-3 in the second.
She received treatment but an emotional Halep was forced to withdraw from the clash, the defending champion handing victory to Kerber.
The Romanian was then helped from the grandstand court, leaving the area with strapping on her leg and a heavy limp, raising doubts about her ability to compete at Roland Garros, where she would likely be one of the favourites.
Earlier Williams made her first appearance on the tour since February, losing the 1,000th match of her glittering career to Nadia Podoroska, who reached the semi-finals in Paris last year.
Podoroska prevailed 7-6 (8-6) 7-5, with 23-time grand slam champion Williams not too downhearted by a defeat to an accomplished clay-court player.
"It's tough to have a first match on clay. It was definitely kind of good to go the distance and to try to be out there, but clearly I can do legions better," Williams said.
"She has a good game, for sure, obviously. She's very consistent. Overall, it was good for me to play such a clay-court player on clay today, but it's a little frustrating. But it's all right. It is what it is.
"I have been training for months, but it feels definitely different on clay to make that last adjustment. Just filling out the game, finding the rhythm. Even sliding and confidence with that, with movement. That's always like a little struggle in the first two matches, and then I'm raring to go."
Osaka has yet to find her footing on clay and the reigning Australian Open champion came up short in the second round as she suffered a surprise loss to Jessica Pegula.
Pegula said after her 7-6 (7-2) 6-2 win: "I know she doesn't love clay, so I just tried to be the clay court player out there today, and it worked just good enough."
World number one Ashleigh Barty had no such difficulties in her 6-4 6-1 over Yaroslava Shvedova, but fourth seed Sofia Kenin was a shock loser to Barbora Krejcikova.
Petra Kvitova was beaten in three sets by Vera Zvonareva but Madrid champion Aryna Sabalenka, last year's French Open champion Iga Swiatek, Elina Svitolina, Karolina Pliskova and Garbine Muguruza all progressed while teenager Coco Gauff knocked out 17th seed Maria Sakkari.
World number one Swiatek sees off Xiyu in Madrid opener
World number one Iga Swiatek overcame Wang Xiyu with the minimum of fuss on Thursday to progress to the third round of the Madrid Open.
Swiatek has yet to win the title in Madrid, which is the only clay-court European event at which the Pole has not triumphed, but she got off to a flying start with a 6-1 6-4 victory over Xiyu.
"I love this place. I got to know the city a little better last year," Swiatek said. "So this time I feel more comfortable around."
Next up for the 22-year-old is a third-round tie against 27th seed Sorana Cirstea on Saturday.
Data Debrief
Swiatek has registered 150 match wins on the WTA Tour since the start of 2022. Elena Rybakina and Coco Gauff are the next best with 108 wins each.
She also became the first player born this century to claim 50 combined match wins in Madrid, Rome and Roland-Garros, since the inaugural women's singles event at the Madrid Open in 2009.
Dominant Gauff double bagels Rus at Madrid Open
Coco Gauff made a flying start to her Madrid Open campaign on Thursday, recording the first double bagel main-draw win of her career as she cruised past Arantxa Rus to reach the round of 32.
Gauff needed just 51 minutes to see off 33-year-old Rus as she booked a meeting with Ukraine's Dayana Yamstremska for Saturday.
The US Open champion lost just 18 points throughout the match – eight in the opener and 10 in the second set – as she put any doubts over her recent form to bed in emphatic fashion.
Gauff's power proved too much for Rus in the opener, the third seed winning 88 per cent of points behind her first serve and converting three of four break points to go a set up in just 23 minutes.
Rus brought up four break points midway through the second set, but when she failed to convert them, Gauff punished her in ruthless fashion by reeling off another three games then finishing things with a terrific forehand winner.
Speaking after her win, the American said: "I played really well today. It was just one of those days for me… 6-0 6-0, I've never done that before, I'll probably never do it again."
Data Debrief: Gauff matches Azarenka, Halep feat
Gauff is just the third player to register a 6-0 6-0 win in the women's singles draw at the Madrid Open, following in the footsteps of two former world number ones in Victoria Azarenka and Simona Halep.
The American, who only turned 20 last month, is also the youngest player to double bagel an opponent in any main-draw match on the WTA Tour since Iga Swiatek did so against Karolina Pliskova in the 2021 Italian Open final in Rome.
Nadal cruises past teen Blanch to tee up De Minaur rematch in Madrid
Darwin Blanch presented little challenge for Rafael Nadal, who dropped just one game in a convincing 6-1 6-0 triumph at the Madrid Open.
Nadal is feeling his way back to fitness, but 16-year-old qualifier Blanch offered little resistance to the 22-time major champion on Thursday.
Making his farewell appearance at the Madrid Open, where he has won five titles, Nadal needed just 64 minutes to progress to round two.
"I think today I played against an opponent with a great future in front [of him], but today, still making mistakes," said Nadal.
"I just tried to be there, be solid all the time without taking a lot of risks. It worked well. I'm happy to be through and I wish him all the very best for the future."
Nadal's reward is a rematch with Alex de Minaur, who he lost to last week in Barcelona.
Data Debrief
This game saw the largest age gap (21 years, 117 days) between two opponents in the history of ATP Masters 1000 events.
Nadal has now registered 57 wins at the Madrid Open, which is 20 clear of any other player.
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