Antibodies to HBsAg of IgG class enhanced the helper activity of a human T cell clone to promote the in vitro synthesis of immunoglobulins by autologous B lymphocytes. Using two different assay systems, the effect of antigen-specific antibodies on the helper function of a HBsAg-reactive T cell clone was studied. The monoclonal antibody to HBsAg A5C3 (IgG) increased significantly the T cell-dependent production of immunoglobulins by Staphyloccocus aureus-stimulated autologous B lymphocytes. Furthermore, the results obtained with a different type of assay showed that A5C3 also increased the synthesis of antibody to HBsAg by the autologous B cells in the presence of HBsAg and the helper T cell clone. On the other hand, when the monoclonal antibody to HBsAg of IgM class, H5D3 or the F(ab′)2 fragment of A5C3 were tested, no significant enhancement of the helper activity of the T cell clone was observed. Experiments performed in mice showed that the in vivo antibody to HBsAg response to low concentrations of HBsAg was significantly enhanced by mixing this antigen with monoclonal antibody to HBsAg of IgG class. No effect was observed when a monoclonal antibody to HBsAg of IgM class was used to prepare the immune-complexed immunogen. The results presented here suggest that antibodies play a critical role in their own production through regulating the activity of helper T cells. This phenomenon might contribute to the increased antibody synthesis of in vivo secondary immune responses and could be of use in designing more efficient vaccine programs in man.