Six baboons were each repeatedly exposed to a total of 700 cercariae, divided into small (trickle) doses, and four of the six received an additional challenge dose of 1,000 cercariae. The levels of various antibodies were measured over the course of their 3- to nearly 4-year infections by the following assays: enzyme-linked immunosorbent assay (ELISA) with anti-baboon µ- and γ-chain conjugates against a soluble adult worm antigen, slide flocculation with cercarial antigen, circumoval precipitation (COP), and “long-term” passive cutaneous anaphylaxis (PCA) with adult worm antigen. Some additional multiply infected baboons were also followed for opsonizing antibodies to schistosomules and by “short-term” PCA for anti-adult worm IgG reaginic antibodies. With respect to anti-adult response measured by ELISA, IgM class antibodies appeared by 4–6 weeks post-infection (p.i.) and peaked at 7–9 weeks (p.i.) Anti-adult IgM class antibodies were maintained over a long span of time, and at higher levels in multiply exposed baboons, in contrast to what was observed (in the accompanying report) in singly exposed baboons. They showed a tendency to increase with accumulated cercarial exposures. Neither IgM nor IgG anti-adult antibodies showed dramatic post-challenge responses. Flocculating cercarial antibodies were unrelated to anti-adult antibodies and were transient in appearance, confirming their unsuitability for diagnosing active infections. COP antibodies were generally present throughout the infection period. Antibodies capable of opsonizing schistosomules in vitro for complement-mediated, baboon peripheral blood leukocyte adherence and damage were measured in three baboons. Their titers were unrelated to anti-adult IgM or IgG class antibodies or to immunity status. IgE and IgG class anti-adult anaphylactic antibodies, measured by long-term and short-term PCA, respectively, were erratic in appearance and persistence. IgE, but not IgG, anti-adult anaphylactic antibodies were related to dermal hypersensitivity as measured by direct skin tests with adult worm antigen. Cercarial dermatitis occurred in baboons which had had prior exposure to the parasite, and its severity was related to the number of cercariae penetrating the site.