Novak Djokovic's bid to become the first man in 43 years to hold all four Grand Slam titles at the same time hit its first hurdle on Friday when Roger Federer became a potential French Open semi-final opponent.
In stark contrast, defending champion Rafael Nadal, bidding for an historic seventh title, was left with a more comfortable passage with third seed Andy Murray, who is struggling with a back injury, as a possible semi-final rival.
World number one Djokovic, three times a semi-finalist in Paris, is the top seed at Roland Garros with Federer, the 2009 champion, seeded three and Friday's draw pitted them in the same, imposing section.
Djokovic starts against Italy's Potito Starace and could face Australia's former world number one Lleyton Hewitt, playing in Paris on a wildcard, in the second round.
Adding spice to the top half of the draw is the presence of dangerous Argentine Juan Martin del Potro, the 2009 US Open winner, who could face Federer in the fourth round.
Ninth seed Del Potro is the only player outside of the big three to have won a Grand Slam title in the last seven years.
Three years ago, the 23-year-old Del Potro took Federer to a five-set thriller in the semi-finals.
Federer starts against Germany's Tobias Kamke with big-hitting David Nalbandian a possible second round foe and Czech Tomas Berdych a potential quarter-final opponent.
Meanwhile, second seed Nadal had every reason to smile as the draw shone kindly on him.
Nadal, who equalled Bjorn Borg's record of six wins here last year, starts against Italy's Simone Bolelli and has claycourt grinders Nicolas Almagro and Juan Monaco also in his quarter of the draw.
The Spaniard could face Serbian eighth seed Janko Tipsarevic in the last eight.
Murray is Nadal's scheduled semi-final opponent, in what would be a repeat of the 2011 last four, and the Scot starts against Japan's Tatsuma Ito.
In the women's draw, top seed Victoria Azarenka begins against Italian Alberta Brianti while world number two Maria Sharapova starts against Alexandra Cadantu of Romania.
Azarenka, twice a quarter-finalist, has an injury concern having been forced to quit her fourth round match in Rome because of a shoulder problem.
Azarenka has US Open winner Samantha Stosur as a possible quarter-final match-up.
Sharapova and 2002 champion Serena Williams could meet in a mouth-watering quarter-final.
Sharapova, a semi-finalist in 2007 and 2011, and Williams are the form players going into Roland Garros.
The Russian won on clay in Stuttgart and Rome while Williams claimed the Charleston and Madrid titles before withdrawing from her Rome semi-final with back pain.
Defending champion Li Na of China starts against Romania's Sorana Cirstea while Williams begins against France's Virginie Razzano.