In this report we compare the effect of stimulation of peripheral mononuclear cells (PBMC) by using two monoclonal antibodies (MoAb) directed against the CD2 receptor on T cells or by using autologous erythrocytes (E) which express on their surface lymphocyte function‐associated antigen 3 (LFA3), a natural ligand for CD2. The addition of autologous erythrocytes to pokeweed mitogen (PWM)‐stimulated PBMC results in ihe enhancement of polyclonal immunoglobulin synthesis and of antigen‐specific B‐cell responses. Because B cells lack the CD2 molecule, it can be concluded that their enhanced activity is a consequence of the delivery of activating signals by activated T lymphocytes. When PBMC cultures were stimulated with a pair of anti‐CD2 MoAb (Leu5b and VIT13) we were able to induce polyclonal immunoglobulin synthesis, particularly IgM, in cultures supplemented wilh interleukin 2 (IL‐2). Specific responses to telanus toxoid (TT) and keyhole limpet haemocyanin (KLH) were also enhanced by the addition of autologous E to PWM‐stimulated PBMC. Significant anti‐TT responses were observed in cultures stimulated with E+TT+IL‐2. In contrast, stimulation of PBMC wilh VIT13+Leu5b+IL‐2+antigen was not effective in inducing anli‐TT antibody and only weakly effective in inducing anti‐KLH antibodies. Replacing Leu5b by anti‐CD3 had no effect on the induction of specific antibody responses; in contrast, replacement of Leu5b by E enhanced anti‐TT antibody production while the effect on polyclonal production of IgM was minimal. Therefore, it appears that the signal delivered by the association of CD2 with LFA3 is a better potentiating signal for specific B‐cell responses than the signal delivered by pairs of MoAb to different epitopes of C