Mice were made B cell-deficient by injections of globulin prepared from goat antimouse mu-chain serum. Anti-mu globulin was administered throughout the experiments (18 or 23 weeks). B cell deficiency was determined at the time of assay of worm burden levels (7 weeks after challenge with Schistosoma mansoni) by quantitation of serum IgM and IgG, by assaying the specific antibody response to cercarial and adult worm antigens in enzyme-linked immunosorbent assay and by histologic examination of the spleen and mesenteric (regional) lymph nodes. Four-week-old mice were exposed to S. mansoni and 8 weeks later were challenged with a second exposure. The B cell-deficient mice developed a degree of resistance (79%) similar to that of the intact controls (81%). The IgM and IgG levels of the B cell-deficient mice were markedly suppressed. Follicular development was not detected in their lymph nodes; but in the spleen of some animals clusters of cells morphologically similar to B cells were observed peripheral to a central T cell-like area. B cell-deficient mice developed schistosome egg granulomas comparable to those of the intact controls. Control animals developed an antibody response with titers of 1:64 to 1:1,024 against cercarial and adult worm antigens; B cell-deficient animals were nonreactive in these assays. The data suggest that specific antibody does not play a major role in resistance acquired within 8 weeks as a result of a primary infection in murine schistosomiasis.