The roles of interleukin (IL)-4 and interferon (IFN)-gamma in Schistosoma japonicum egg granuloma formation were investigated in cercariae-infected (infection model) or after implantation of laid parasite eggs (egg implantation model) in cytokine deficient mice. Two weeks after hepatic egg-implantation, a markedly decreased mononuclear cell infiltration and lack of multinuclear cell formation were characteristic features in IL-4 deficient mice. By 4 weeks (late stage), the cellular reactions around the eggs were negligible in the deficient mice. Compared to the controls, there was a drastic reduction in the production of the Th2 cytokines, IL-4, IL-5 and IL-13. MCP-1 levels were also significantly lowered. In mice experimentally infected with cercariae, granuloma cellularity in both the wild-type and IL-4 deficient mice at 45 days and 10 weeks postinfection was analogous to the egg implantation model at 2 and 4 weeks. Overall, the effects of IFN-gamma deficiency on granuloma induction differed markedly from the IL-4 results. Two weeks after egg implantation, IFN-gamma deficient mice showed suppressed neutrophil response and hepatic necrosis with confluent mononuclear cell infiltration along the outer layer of granulomas. By 4 weeks, there was a decrease in cell infiltration, fibrosis and MCP-1 production while IL-10 production increased. While these early characteristic features for IFN-gamma deficiency were common to both the egg implantation (at 2 and 4 weeks) and cercariae infection model (at 45 days), there was a surprising difference, i.e. marked fibrosis was found in the late stages (at 10 weeks postinfection) of cercariae-infected mice, but not in parasite egg implanted mice. Furthermore, while IL-13 levels were unchanged, both MCP-1 and IL-4 production were significantly lower at 10 weeks in comparison with wild-type. The present study clearly demonstrates the importance of both Th1 and Th2 cytokine responses in S. japonicum egg-induced granuloma formation.