Roberto Bautista Agut and John Isner reached the Winston-Salem Open third round as Fernando Verdasco and Gilles Simon crashed out.
Bautista Agut, last year's runner-up and the top seed at the ATP 250 event, was too good for Dusan Lajovic 6-4 6-3 on Tuesday.
Two-time champion Isner, who has won titles at Newport and Atlanta in recent weeks, sent down 13 aces in his 2-6 7-6 (7-5) 6-3 win over Andrey Kuznetsov.
There were seeds aplenty in action, with Steve Johnson, Borna Coric, Chung Hyeon and Paolo Lorenzi also advancing.
Johnson cruised past Lu Yen-hsun 6-4 6-3, Coric downed Donald Young 4-6 6-4 6-2, Chung claimed a 5-7 6-1 6-1 win against Andrey Rublev and Lorenzi got past Thiago Monteiro 2-6 6-4 6-4.
Several others departed, including top-10 seeds Pablo Carreno Busta, Verdasco, Simon and Yuichi Sugita.
Defending champion Carreno Busta was beaten by 2011 runner-up Julien Benneteau 7-6 (7-5) 6-7 (5-7) 6-3.
Verdasco was stunned by Horacio Zeballos 3-6 7-5 6-4 and Simon went down to Damir Dzumhur 6-4 1-6 6-4.
Sugita was outclassed by talented American teenager Taylor Fritz 6-3 6-2.
Meanwhile, there were wins for Andreas Seppi, Carlos Berlocq, Kyle Edmund and Marton Fucsovics.