Concanavalin A (Con A), antilymphocyte serum (ALS), and the allogeneic effect have all been shown to enhance antibody responses to thymus-independent (TI) antigens by a T cell-dependent mechanism. Enhancement presumably involves an effect on the responding B cells by amplifier T cells (TA) that are activated by the particular agent used, i.e., Con A, ALS, or allogeneic cells. In the present study the ability of these agents to augment antibody responses to TI-1 and TI-2 antigens was compared. It was found that antibody responses to TI-2 antigens were markedly enhanced by allogeneic cells or ALS given with antigen. Antibody responses to TI-1 antigens were in all cases unaffected. Because TI-1 and TI-2 antigens primarily stimulate separate subpopulations of B cells, these results suggest the B cell subset that responds to TI-1 antigens, i.e., Lyb-5-negative B cells, may not be responsive to signals from nonspecifically activated TA. This conclusion was further supported by experiments demonstrating that responses to TI-2 antigens could not be enhanced in mice that have only Lyb-5-negative B cells, i.e., CBA/N x BALB/c F1 males, and that responses to a T-dependent antigen (HRBC) could be augmented by the allogeneic effect in normal mice but not in mice lacking Lyb-5-positive B cells.