AbstractA modified splenic fragment assay was used to assess the role of antigen‐specific helper T cells in B cell isotype expression. Limiting numbers of carrier‐specific helper T cells from lines or clones were injected along with a source of B cells into lethally irradiated unprimed recipients. The incidence of lodging of the T cell lines in recipient spleens at 18 h was determined by autoradiography to be 1.5 to 4.3% of the injected cells. These T cells were necessary and sufficient for the generation of T‐dependent B cell responses within splenic fragments culturedin vitrowith specific antigen. A comparison of isotypic responses from splenic and Peyer's patch B cells generated with the same T cell population revealed that a high proportion of the response from Peyer's patch B cells consisted of IgA antibody exclusively (46–57%) while the percentage of such responses from splenic B cells was much lower (7–10%). Thus, the isotype pattern of the response reflected the B cell source. Experiments in which cloned hemocyanin‐specific T cells provided help to T‐depleted spleen cells within splenic fragments from athymic recipients indicated that a single specificity of helper T cell is both necessary and sufficient to support the generation of antibody responses consisting of multiple isotypes. Isotype‐specific T cells do not appear to be required