CD45 exon 6-deficient mice show a profound block of thymocyte development at a transitional differentiation step from immature CD4+ CD8+ to mature single-positive cells. Only a few T lymphocytes are observed in the periphery of such animals, but B cell development is not affected. We investigated whether mature B lymphocytes in CD45 exon 6-deficient mice have normal functions in the absence of CD45 expression and show here that CD45-defective B lymphocytes from CD45 exon 6-deficient mice have intact B lymphocyte functions, including T-dependent and T-independent antigen-specific antibody production and class switching in vivo if normal CD4+ T lymphocytes were adoptively transferred into the mutant mice. From these results, we conclude that CD45 expression on B lymphocytes is not essential for B cell responses following antigen stimulation in vivo. However, CD4+ T helper function was severely diminished in CD45 exon 6-deficient mice, suggesting that the requirements of CD45 molecules in antigen-specific response and development are different between T and B lymphocytes.