We have demonstrated that carpet shell clam (Ruditapes decussatus) hemocytes produce nitric oxide (NO) in response to zymosan or bacterial lipopolysaccharide (LPS). This NO production was partially inhibited by the NO synthase inhibitor, N-omega-nitro-L-arginine (L-NAME). The capability of clam hemocytes to produce NO in response to the bacterial pathogen Vibrio tapetis was also studied. Incubation with bacteria induced a significant NO production by clam hemocytes, even though exogenous NO only slightly decreased the growth of V. tapetis. The effect of exogenous NO on the capability of clam hemocytes to phagocytose labeled Escherichia coli was studied using two different NO donors S-nitroso-N-acetyl-penicillamine (SNAP), and diethylenetriamine NO adduct (DETA/NO). Exogenous NO did not increase hemocyte phagocytosis, indicating that NO does not mediate phagocytosis in this species. These results are in accordance to those observed in other mollusk species, in which NO was independent of phagocytosis and constitutes an alternative method of killing invading pathogens.