Splenic involvement in murine schistosomiasis mansoni is manifested by splenomegaly, hyperplasia of the lymphoid and mononuclear phagocytic elements, and strong immune responses of splenic lymphocytes to schistosome antigens. In the present study, groups of Schistosoma mansoni-infected mice were splenectomized or sham treated at 1, 4, and 8 weeks of the infection, and at 12 weeks changes in pathophysiology, humoral, and granulomatous responses as well as liver fibrosis were examined. Splenectomy had no influence on the body and liver weight or portal pressure of the infected mice. Mice which underwent splenectomy at 8 weeks developed anemia. Whereas splenectomy performed at 8 weeks of the infection did not affect the anti-schistosome egg antigen humoral response of the animals, it caused significant enhancement in the liver granulomatous reaction. Increased granuloma size did not result in a concomitant increase in the extent of liver fibrosis as measured by hydroxyproline content. It is concluded that the spleen may play an important role in the immunoregulation of the egg-specific granulomatous inflammatory response.