New York: Defending champion Novak Djokovic and fellow two-time winner Rafael Nadal take centre stage on the Arthur Ashe Stadium on Wednesday looking to seal third round spots.
World number one Djokovic, who needed treatment on a right upper arm injury during his laboured four-set win over Poland's Jerzy Janowicz on Monday, faces Jiri Vesely of the Czech Republic.
Vesely inflicted a rare defeat on the Serb when he triumphed on clay at Monte Carlo in April.
"Different surface, different circumstances, best-of-five. But still, Vesely deserves respect," said Djokovic, the 2011 and 2015 champion in New York and looking for a third major of the year.
"He has a big game, big serve, big forehand, and moves well for his size. So let's see. Conditions are quite suitable to my style of the game. Hopefully I'll be able to slow his serve down a little bit and then take it from there."
Spanish fourth seed Nadal, the 2010 and 2013 champion, takes a 7-1 career record over Italy's Andreas Seppi into their night time clash.
Seppi, ranked at 87, has never got beyond the third round in New York but he is a former top 20 player who knocked Roger Federer out of the Australian Open two years ago.
Two-time Wimbledon champion Petra Kvitova gets play underway on Ashe against Turkey's Cagla Buyukakcay followed by Caroline Wozniacki, twice a runner-up in New York, facing former US and French Open champion Svetlana Kuznetsova.
Reigning Roland Garros champion and third seed Garbine Muguruza of Spain tackles Latvia's Anastasija Sevastova.
Muguruza needed three sets to see off Belgian qualifier Elise Mertens in a first round tie which also saw her need a medical timeout after suffering heat exhaustion.
Angelique Kerber, the second seeded Australian Open champion who could depose Serena Williams as world number one, faces 34-year-old Mirjana Lucic-Baroni.
The veteran Croatian made the last 16 in 2014 having played her first US Open back in 1997.
Italian seventh seed Roberta Vinci, last year's runner-up, faces Christina McHale of the United States.
Also on Louis Armstrong are US number one John Isner against Belgian qualifier Steve Darcis while compatriot Jack Sock clashes with German qualifier Mischa Zverev.
Two highly-fancied potential title winners are also in second round action. Canadian fifth seed Milos Raonic, the Wimbledon runner-up, plays Ryan Harrison of the US.
In the women's draw, American eighth seed Madison Keys meets 16-year-old compatriot Kayla Day.
