Nick Kyrgios could face Rafael Nadal in a blockbuster third-round clash at the Madrid Masters on Thursday after easily seeing off the American Ryan Harrison 6-3, 6-3. Nadal begins his quest for a fifth title in Madrid later Wednesday against Italy's Fabio Fognini.
Kyrgios and Nadal have only met twice with the Australian making his breakthrough with a four-set win over the 14-time Grand Slam champion at Wimbledon in 2014.
Nadal, though, edged their only previous meeting on clay at the Rome Masters last year.
Fifth seed Milos Raonic is also into the last 16 as he got the better of a battle between two big servers 6-4, 6-4 over Gilles Muller.
Raonic will face Belgium's David Goffin next.
Kei Nishikori recovered from a dreadful start to beat Argentine Diego Schwartzman 1-6, 6-0, 6-4.
The world number eight has made at least the semi-finals in each of the last three years in Madrid and will face David Ferrer in round three.
Ferrer didn't have to hit a ball as Jo-Wilfried Tsonga withdrew with a shoulder injury.
"The problem is I stretch a muscle in my shoulders. I don't want to take any risk," said Tsonga with just over a week to go until the start of the French Open.
World number two Novak Djokovic begins life without long-term coach Marian Vajda later against Nicolas Almagro.
In the WTA Madrid Open, Svetlana Kuznetsova remained one of only three of the top 10 seeds left in the draw with a 6-4, 7-5 win over Wang Qiang to reach the quarter-finals.
Kuznetsova will face the winner of an intriguing clash between top seed Angelique Kerber and Eugenie Bouchard, who dumped out Maria Sharapova in thrilling fashion on Monday.
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