Helper T cells directed to B cell surface determinants activate their "targets" into polyclonal antibody production in vitro and in vivo, but B cells which bind to epitopes on the helper cell surface are preferentially induced. Furthermore, "anti-helper" B cell activation also occurs by "back-stimulation", that is even when the responding B lymphocytes are not specific targets for the inducing helper cells, as long as these are simultaneously activated by appropriate interactions with presenting cells. In our experimental systems, this is the only condition where "bystander" activation can be recorded. These findings suggest mechanisms of auto-antibody production associated with unrelated helper cell activity in vivo.