The aim of this study was to characterize the effects of rebamipide on the oxidative burst of human neutrophils. The neutrophil oxidative burst was measured in the presence of rebamipide and cimetidine using lucigenin- or luminol-dependent chemiluminescence (LgCL or LmCL). Rebamipide inhibited the LmCL response stimulated with opsonized zymosan, 12-myristate 13-acetate phorbol, and calcium ionophore in a dose-dependent manner, but the LgCL response was inhibited when neutrophils were stimulated with opsonized zymosan. LmCL response was also dose-dependently attenuated by rebamipide even in the presence of cimetidine. Thus, addition of rebamipide to H(2)-receptor antagonists can be considered for the treatment of gastric mucosal injury associated with oxidative stress.