World number one Victoria Azarenka suffered a blow to her French Open preparations when she was forced to pull out of the Italian Open with a right shoulder injury on Wednesday, but an aching Roger Federer gingerly advanced to the third round.
Azarenka had shown no sign of discomfort when she walloped Israel's Shahar Peer 6-1 6-2 in the second round but the WTA announced her withdrawal shortly after the victory to the surprise of everyone in the Foro Italico.
With just 10 days until the start of the French Open, the Belarusian will hope for a quick recovery ahead of her bid for a second straight grand slam title.
In-form Federer, carrying a few aches and pains after winning the Madrid Masters on Sunday, saw off Carlos Berlocq of Argentina 6-3 6-4.
The Swiss only decided to play after his morning practice session.
"I wanted to see how I felt and make sure that I didn't have anything major because we're ahead of a long summer," he said.
"If this was the last tournament of the season it would be no problem. But as this is the beginning of many tournaments in a row, potentially a lot of five-setters in a row, I need to make sure I make good decisions, so I go round by round.
"I'm happy that I felt OK out there today."
Nadal, beaten in the third round in Madrid, looked far more comfortable as he eased to a 6-1 7-5 win over German Florian Mayer.
Mayer beat Nadal the last time they played, in Shanghai last year, but on his favoured clay, the Spaniard never allowed him to get a foothold in the match.
"It is an important victory," Nadal said. "In the first set I played aggressively. Mayer put me in difficulty with his serve but I don't think I ever suffered."
Tomas Berdych, beaten by Federer in the Madrid final, eased past Lukas Kubot 6-4 6-1 to reach round three, while Juan Martin Del Potro also advanced.
But American John Isner was upset 2-6 7-6 7-5 by Italian Andreas Seppi.
Azarenka's withdrawal handed Dominika Cibulkova of Slovakia a free ticket to the last eight, but Serena Williams had to battle back to beat Russia's Nadia Petrova 4-6 6-2 6-3 in the American's second match in 18 hours.
"When I saw the schedule, I said, 'Oh my God, are you serious?" Williams told reporters. "But that's life. You just have to be able to adjust and I was really happy I was able to come through."
Her sister Venus improved her chances of making the Olympics on merit as she battled to a 7-6 6-1 win over Ekaterina Makarova of Russia.
The former world number one, who needs to climb above Varvara Lepchenko in the United States pecking order, will next take on fifth seed Sam Stosur of Australia.
World number three Agnieszka Radwanska lost 6-4 4-6 6-1 to Czech Petra Cetkovska, while former world number one Wozniacki, suffering from sinus problems, quit when trailing 6-4 4-0 to Anabel Medina Garrigues of Spain.