The role of CD4+ T cells in the gastrointestinal (Gl) 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 in both IgA effector (lamina propria regions of the intestine; LP) and inductive (Peyer’s patch; PP) sites. However, levels of CD3+CD4CD8+ and CD4CD8 (double negative) T cells remained constant or Increased. When sections of small intestine were assessed for the isotype of lg-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-positive (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. © 1991 Oxford University Press.