We investigated the involvement of nitric oxide in Schistosoma-induced liver injury. We found that inducible nitric oxide synthase mRNA became detectable in the liver at the onset of parasite egg laying and levels then increased as the eggs accumulated in the organ. Enzyme concentration and activity paralleled mRNA levels. The event was a direct effect of egg deposition, as it occurred in the liver after natural infection, or in the lungs after i.v. injection of the eggs. However, nitric oxide seems to have no direct effect on the eggs since in vitro assays showed that the nitric oxide donor SIN-1 did not alter the ability of the eggs to hatch. L-Arginine and L-NAME, a nitric oxide synthase inhibitor, were administered to infected mice in an attempt to increase or reduce nitric oxide production, respectively. Arginine had no effect on the disease, whereas the inhibitor led to a marked decrease of hepatic injury with, in particular, reduced fibrosis and decreased lipid peroxidation. In conclusion, not only is inducible nitric oxide synthase activity unlikely to exert an anti-microbicidal effect against the egg stage of S. mansoni but it might lead to deleterious effects in the liver and therefore contribute to the pathology.