Over the past decade, nitric oxide has been intensely studied due to its relevance as a widespread intra- and intercellular messenger and as a cytotoxin released during several physiopathological events, including immunological reactions and inflammation. In the present paper, we investigate the effect of inhibition of NO synthesis, using an analogue of L-arginine, N omega-nitro-L-arginine methyl ester (L-NAME), on in vitro granulomatous formation of human peripheral blood mononuclear cells (PBMC) from Schistosoma mansoni-infected individuals. The results demonstrated that human PBMC are capable of in vitro NO production and that inhibition of its production through the addition of L-NAME is responsible for exacerbating granulomatous reaction. This L-NAME-induced granuloma enhancement (ranging from 30 to 65%) was measured using the granuloma index. Furthermore, we observed a general time-dependent increase in NO production during the period of cell culture (21 days) and an inverse relationship between nitrite detection and granuloma reactivity. Collectively, our results point to a possible regulatory role of NO on the development of granulomatous inflammation.