In this study the efficiencies of a monoclonal anti-idiotopic (Id) antibody (anti-Id498) and of various preparations of nominal antigen in the induction of an antigen-specific human B cell response in vitro were compared. Anti-Id498 recognizes a recurrent, binding site-related Id present on IgM antibodies with specificity for N-acetyl-D-glucosamine, the immunodominant group of streptococcal group A carbohydrate (A-CHO). We have previously shown that anti-Id498 induces IgM anti-A-CHO secretion from B cells of donors that possess Id-498+ antibodies in their serum. A-CHO was presented to B cells either in soluble or insoluble form, i.e. coupled to beads or as intact bacteria. Purified blood B cell populations from three Id+ healthy donors with high numbers of circulating anti-A-CHO B cells were used and antibody-producing B cells are enumerated in a single-cell assay (spot ELISA). The data show that anti-Id498 was superior in the induction of IgM anti-A-CHO-secreting B cells in two donors (factor 4.6 and 13.5 as compared to the most efficient antigenic stimulation). In the third donor antigen stimulation was slightly more efficient than anti-Id but only with Sepharose-bound A-CHO and not with soluble A-CHO or intact bacteria. The increase of specific B cells induced after stimulation with anti-Id498 could be abolished after addition of autologous T cells in two donors. On the contrary, an enhancement of the specific response was observed after addition of autologous T cells in antigen-stimulated cultures. Neither suppression nor enhancement were induced by addition of irradiated T cells.