The feasibility of selectively eliminating human antigen-specific B cell responses by treating cells in vitro with antigen covalently linked to a cell toxin was examined. Tetanus toxoid (TT) was conjugated to the toxin ricin via a thioether linkage. Peripheral blood mononuclear cells from recently immunized subjects were preincubated for 2 h with TT-ricin in the presence of lactose. Antigen was then removed, and the cells from recently immunized subjects were preincubated for 2 h with TT-ricin in the presence of lactose. Antigen was then removed, and the cells were stimulated with pokeweed mitogen to induce antibody production. TT-specific antibody production was completely abrogated by preincubation with TT-ricin but not by TT alone or a mixture of TT and ricin. In contrast, polyclonal immunoglobulin production was not diminished by TT-ricin. This selective abrogation was also seen when B cells alone were preincubated with TT-ricin and a source of T cell help was later provided. T cell blastogenic responses to TT remained intact after TT-ricin exposure. Thus, antigen-toxin conjugates are capable of selectively eliminating specific antibody-producing B cell clones, while leaving intact the remainder of the B cell repertoire.