Detailed parasitologic, serologic, clinical, and pathologic observations of Schistosoma mansoni infections in the chimpanzee were made over a period of 3 years. Six animals were exposed once to 250, 1,000, or 2,000 cercariae and necropsy was performed after 7 to 36 months. Four other chimpanzees were exposed monthly to 100 or 250 cercariae and necropsy was performed 24 to 36 months after the first exposure. Viable eggs were found in the feces 6 to 8 weeks after exposure and without significant reduction in number for the duration of the experiment. Recovery of worms revealed no evidence of acquired immunity with time or repeated exposures. Although the relation of recovery of worms to fecal egg counts and tissue egg assays was variable, there was a direct relation between the severity of clinical and pathologic involvement and the magnitude of egg deposition in tissues. Pathologic changes in the liver of the chimpanzee were remarkably similar to those reported for heavily infected human beings. In one animal characteristic pipe-stem fibrosis and extensive portal-systemic collateral circulation developed, with esophageal varices. Fibrosis of distal portal fields occurred around granulomata and egg-related inflammatory infiltrates. In middle-sized and larger portal fields, stage 3 pipe-stem fibrosis was found to precede local egg deposition and is of uncertain pathogenesis. Severe pathology of the colon with extensive development of inflammatory pseudopolyps was also seen. These experimental infections in chimpanzees closely resembled Manson's schistosomiasis in man as regards the course of the disease and the number and location of worms and eggs.