Groups of 6 to 8 grivet monkeys (Cercopithecus aethiops aethiops), each of which had been exposed to 600 cercariae of Schistosoma mansoni, were killed 3, 6, and 31 months after exposure. Other groups of monkeys were repeatedly challenged with cercariae beginning 4 or 23 months after the initial infection, and were killed 31 months after the first exposure. Peripheral blood leukocytes, eosinophiles, and schistosome eggs passed in the feces were determined during the course of the infection. At autopsy, gross and histopathologic observations were made, worms were recovered by perfusion, and the number of eggs in the tissues was determined by digestion. Monkeys became acutely ill about 8 weeks after the initial exposure, and death was attributed to acute “toxemic” schistosomiasis in 4 of 46 infected animals. The symptoms and signs of the acute phase did not recur with reinfection. Most subsequent natural deaths were caused by Klebsiella infection, which occurred in both infected and control monkeys and did not appear to be related to the schistosome infection. Relatively stable infections were found after a single exposure to cercariae, with only a slight decrease in worm numbers and moderate decrease in egg passage after 31 months. With repeated reinfection, only 19% of challenge cercariae developed into adult worms. Oviposition by these worms was delayed and the rate of oviposition was substantially less than in monkeys infected only once. Eggs deposited in the tissues were rapidly destroyed. The calculated rate of oviposition varied from 658 eggs/day per female 3 months after a single infection to 299 eggs/day per female 31 months after repeated infections. Although very heavy infections were present in repeatedly infected monkeys, only slight hepatic fibrosis was seen and no portal hypertension or portal-systemic collateral circulation developed. Severe intestinal disease was present in only two monkeys. The remaining animals had little diarrhea after the acute phase, and there was only slight loss of plasma protein into the feces 31 months after exposure.