Resveratrol is a dietary phytochemical that has been shown to inhibit proliferation of a number of cell lines and behaves as a chemopreventive agent in assays that measure the three stages of carcinogenesis. We tested for its chemopreventive potential against gastric cancer by determining its interaction with signaling mechanisms that contribute to the proliferation of transformed cells. Low levels of exogenous reactive oxygen (H₂O ₂) stimulated ³H-thymidine uptake in human gastric adenocarcinoma SNU-1 cells, while resveratrol suppressed both synthesis of DNA and generation of endogenous O₂^-, but stimulated NOS activity. To address the role of NO in the antioxidant action of resveratrol we measured the effect of SNP, a NO donor, on O₂^- generation and on ³H-thymidine incorporation. SNP inhibited DNA synthesis and suppressed ionomycin-stimulated O₂^- generation in a concentration dependent manner. Our results reveal that the antioxidant action of resveratrol toward gastric adenocarcinoma SNU-1 cells may reside in its ability to stimulate NOS to produce low levels of NO, which in turn, exert antioxidant action. Resveratrol-induced inhibition of SNU-1 proliferation may be partly dependent on NO formation, and we hypothesize that resveratrol exerts its antiproliferative action by interfering with the action of endogenously produced reactive oxygen. This data is supportive of the action of NO against reactive oxygen and suggests that a resveratrol-rich diet may be chemopreventive against gastric cancer.