We have previously demonstrated that CD4⁺ suppressor T cells (T_s) inhibit the secretion of interferon (IFN)‐γ, but not interleukin (IL)‐2, by effector cells of experimental autoimmune encephalomyelitis (EAE). Moreover, CD4⁺ T_s appear to regulate IFN‐γ by secretion of transforming growth factor‐β. We now show that CD4⁺ T_s produce a lymphokine with IL‐4 activity in response to a determinant associated with EAE effector cells. CD4⁺ T_s do not proliferate or secrete IFN‐γ, IL‐2, or IL‐4 in response to myelin basic protein, nor do CD4⁺ T_s proliferate or secrete IL‐2 when co‐cultured with irradiated EAE effector cells. Rather, CD4⁺ T_s secrete IL‐4 when co‐cultured with either irradiated effector spleen cells or irradiated encephalitogenic line cells. CD4⁺ T_s do not secrete IL‐4 in response to OVA‐primed spleen cells, suggesting that the suppressor cells recognize a determinant specific to encephalitogenic T cells. Furthermore, CD4⁺ T_s secrete IL‐4 when cultured with synthetic T cell receptor (TcR) V_β8, but not TcR V_β14 peptide, in the presence of antigen‐presenting cells. This response is major histocompatibility complex class II restricted as demonstrated by inhibition of the response with anti‐class II monoclonal antibody. These results suggest that CD4⁺ T_s recognize a determinant associated with TcR on the surface of EAE effector cells and respond by secreting IL‐4, in a manner analogous to the T_h2 lymphocyte subtype.