Resveratrol (3,4',5-trihydroxystilbene), a natural polyphenol found in red grapes, berries and peanuts, exhibits anti-inflammatory, cell-growth modulatory, and anticarcinogenic effects. In this report, we show that resveratrol inhibited cholera toxin (CT)-induced cyclic AMP accumulation in Vero cells. Resveratrol suppressed the CT activity by suppressing the internalization of CT and traffic to the Golgi apparatus without affecting CT binding to cells. Further, resveratrol partially precipitated CT from solution, and suppressed CT ADP-ribosyltransferase activity. These data suggest that resveratrol may inhibit CT-induced activity directly by associating with CT and suppressing its enzymatic activity, and indirectly by inhibiting CT endocytosis into cells.