A series of benzothiazolium compounds were identified as novel classes of inhibitors of nitric oxide production in a cell culture system. They exhibited approximately 1600 folds potency with IC(50) at approximately 50nM to several microM as compared to IC(50) 88.4microM of l-NMMA, a known inhibitor of nitric oxide synthase. The mechanistic studies suggest that decreased iNOS protein synthesis and mRNA transcription, at least in part, were related to the inhibitory activity of effective benzothiazolium compounds. The correlation of in vivo and in vitro activities using mouse paw edema model was also demonstrated.