Isner knocked off Donald Young in their second-round encounter 7-6 (7-3), 6-4 and Stepanek outfought Ryan Sweeting 4-6, 6-3, 7-6 (7-4).
Isner will take on Jurgen Melzer in the quarterfinals after Melzer rallied for a 2-6, 6-3, 7-6 (7-5) decision over Ivan Dodig.
Stepanek's opponent in the next round will be Sam Querrey, who defeated Kevin Anderson 7-6 (7-4), 6-4.
In other second-round matches Thursday, Benjamin Becker got past Xavier Malisse 7-6 (7-4), 6-4; Lukasz Kubot defeated Philipp Petzschner 7-6 (7-5), 6-2; and Oliver Rochus was a 6-4, 7-5 winner over Ryan Harrison.
No. 2 seed Andy Roddick was eliminated in the first round by Malisse.
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