The immune responses in random-bred Sherman and inbred Lewis and ACI rats exposed to a standard dose of 1,000 cercariae of a Puerto Rican strain of Schistosoma mansoni were evaluated. Worm burdens rose to a maximum by the 4th week of infection, and by the 8th week had declined to very low levels. Some protective immunity was conferred by infection and was demonstrable when challenge exposure occurred as early as 4 weeks after initial exposure. Using a battery of 5 serologic tests and passive cutaneous anaphylaxis, sera were evaluated from time of exposure to 23 weeks after infection. Sherman rats infected with S. mansoni had antibodies demonstrable by the indirect hemagglutination test (IHA) and passive cutaneous anaphylaxis (PCA) test 4 weeks after exposure. However, titers obtained by complement fixation, bentonite flocculation, cercarienhiillen reaktion, or circumoval precipitin tests rose to high levels after the decline in worm burden. Animals sensitized to S. mansoni antigen by use in PCA tests developed IHA antibodies only. Previous studies of Schistosoma mansoni infections in the rat revealed this host to be refractory to massive infection (Koppisch, 1937; Krakower et al., 1940; Cram and Files, 1947; Moore et al., 1949; Stirewalt et al., 1951; Thompson, 1954; Kuntz et al., 1954). Stirewalt et al. (1951), Ritchie et al. (1963a), and Smithers and Terry (1965a, b) reported a decline in worm burden of infected animals between the 4th and 8th weeks after exposure. Warren and Peters (1967) showed that, although the same number of cercariae penetrated the skin of the rat, hamster, mouse, guinea pig, and rabbit, the number of worms that had developed by the 4th week after exposure was the lowest in the rat (26% compared with 37 to 50% for the other animals). By the 8th week the worm burden had fallen to 4% compared with 17 to 64% for other hosts. The mechanism of the reduction of worm burden in the rat has not been adequately studied. The loss of worms resembles the phenomenon described by Stoll (1929) for Haemonchus contortus infection in lambs. The classical self-cure reaction requires the trigger of reinfection and the antigenic stimulation of the molting larvae to initiate the process of worm elimination (Soulsby, 1960). The mechanism of this response in the lamb resembles a hypersensitivity reaction of Received for publication 9 December 1969. the immediate type (Soulsby, 1966). However, not all self-cure phenomena require reinfection to initiate response on the part of the host. In Nippostrongylus brasiliensis infections in rats, worm decline takes place in the absence of reinfection (Mulligan et al., 1965). The mechanism of this response appears to be unrelated to reaginic antibody (Ogilvie and Jones, 1968) but associated with antibodies and alterations of the intestinal wall (Barth et al., 1966). In the present study, baseline data were obtained on the worm burden and serologic response in normal, reexposed rats infected with S. mansoni and antigen-sensitized animals. MATERIALS AND METHODS Random-bred Sherman rats were raised in our laboratory. Inbred Lewis and ACI animals were obtained from Microbiological Associates.* The rats were of either sex and weighed 150 to 200 g. The technique of Smithers and Terry (1965a) was used to expose rats to 1,000 cercariae of a Puerto Rican strain of S. mansoni. Rings placed on the shaved abdominal surfaces of the rats held the cercarial suspension during exposure. At selected intervals from the 2nd week through the 23rd week after exposure, a minimum of 5 rats were bled and autopsied. The number of Sherman rats in this series was 133. Worm burdens in the liver and mesenteric veins were determined by severing the hepatic vein and perfusing with citrate-saline * Use of trade names is for identification only and does not constitute endorsement by the Public Health Service or by the U. S. Department of Health, Education, and Welfare.