The ability of various cell populations to bind and present the thymus-independent antigen TNP-Ficoll to a responding cell population was assessed. The in vitro antibody response to TNP-Ficoll depends upon the presence of B lymphocytes and plastic-adherent accessory cells, but does not require T lymphocytes. Purified B cells were the most effective population in binding and presenting TNP-Ficoll, and adherent cells did not perform this function. Antigen binding and presentation was antigen specific and could be blocked with anti-mu antibody, but not by antibodies directed against other immunoglobulin classes. Spleen cells from mice genetically unresponsive to TNP-Ficoll (CBA/N X BALB/c F1 males) were equally effective as normal spleen cells in antigen binding and presentation. We conclude that the initial events in the induction of the antibody response involves antigen binding by B cells, and that subsequent activation of the subset of B cells that can respond to TNP-Ficoll proceeds either via B cell-B cell interaction or B cell-dependent transfer of antigen to macrophage-like cells.