The role of CD4+ T cells in the gastrointestinal (G1) immune system in vivo was studied in mice selectively depleted of this subset by treatment with monoclonal anti-L3T4 (GK1.5) mAb. Treatment of young BALB/c mice with weekly injections of antl-L3T4 mAb resulted in a selective depletion of CD4+ T cells inboth IgA effector (lamina proprla regions of the intestine; LP) and inductive (Peyer’s patch; PP) sites. However, levels of CD3+ CD4−CD8+ and CD4−CD8− (double negative) T cells remained constant or increased. When sections of small intestine were assessed for the isotype ofIg-containing cells, normal mice contained predominantly IgA plasma cells with small numbers of IgM and IgG plasma cells while antl-L3T4 treatment dramatically reduced the numbers of IgA plasma cells. When numbers of IgA-producing cells were assessed by the isotype-specific ELISPOT assay, the LPL of antl-L3T4 mAb-treated mice showed an 80% reduction In the number of IgA spot-forming cells. The effect of anti-L3T4 mAb treatment on IgA Inductive sites was also studied and this treatment reduced the overall size of PP as well as the germinal centers in this tissue. Although anti-L3T4 treatment depleted CD3+ CD4+ T cells in PP, the relative frequency of surface IgA-posltive (slgA + ) B cells in this tissue did not change. These results show that repeated injection of antl-L3T4 mAb results in a CD4+ T cell deficiency In both IgA inductive (PP) and effector (LP) sites. The depletion of CD4+ T cells resulted in reductions In the numbers of mature IgA plasma cells present in the LP of gut-associated tissues, and reduced the overall size of PP including germinal centers, but did not affect the frequency of slgA+ B cells in this IgA inductive site.