IgG-anti-tetanus toxoid producing B cell precursors from recently immunized individuals can be stimulated by pokeweed mitogen and T cells to produce IgG-Tet antibodies in vitro. Treatment of these cells with tetanus toxoid selectively inhibits the synthesis of IgG-Tet. Because the IgG-Tet precursors display heterogeneity in their surface isotypes (μ, δ, γ), the aim of this study was to determine the surface isotype responsible for transmitting this antigen-induced inhibitory signal to the B cell. B cells were fractionated by rosetting techniques on the basis of surface IgM or IgD. The 4 resulting B cell subsets (sIgM+, sIgM-, sIgD+, sIgD-) were found to be equally susceptible to antigen-induced inhibition. Experiments were then performed with anti-isotype antibodies to investigate further the roles of sIgM, sIgD, and sIgG in antigen inhibition. Treatment of peripheral blood lymphocytes with 10 μg/ml of anti-γ antibody inhibited IgG-Tet antibody production, whereas the addition of up to 100 μg of anti-μ or anti-δ antibodies did not. Tetanus toxoid and anti-γ antibody inhibition of IgG-Tet synthesis in vitro followed similar temporal kinetics, with the IgG-Tet precursors being sensitive to inhibition by either tetanus toxoid or anti-γ antibodies during the first 3 days of culture and not becoming totally resistant to these agents until day 5 of culture. Capping off sIgG receptors, with the subsequent addition of tetanus toxoid, abolished the antigen-induced inhibition of IgG-Tet seen previously, whereas capping off of sIgD or sIgM did not affect antigen inhibition of IgG-Tet antibodies. These results implicate sIgG molecules as those responsible for rendering IgG-Tet precursors susceptible to antigen-induced inhibition.