AbstractB cells could be stimulated to proliferate by mitomycin C‐treated normal T cells that were activated by rabbit anti‐mouse brain antiserum (RaMBr). The B cell proliferation peaked 48 h after the initiation of the cultures. The T cell subset involved was Lyt‐1+, 2−. The B and T cells participating in the interaction did not need to be matched at the H‐2 locus. A long‐term T cell line (C.1.a), which was genetically restricted by the H‐2 complex in its antigen (ovalbumin)‐specific interaction with B cells, could also be induced by RaMBr to stimulate B cell proliferation. However, the RaMBr‐mediated interaction of C.1.a with B cells was genetically unrestricted. This suggests that T cell activation by RaMBr can bypass the requirement for the recognition of I region antigens, which is a feature of antigen‐specific interactions between T and B cells. In fact, RaMBr antibody appeared to function by bringing T cells into contact with B cells by the interaction of the B cell surface membrane Fc receptors with the Fc portion of RaMBr antibody bound to the T cell surface. Brain‐associated antigen(s) appeared to play a unique role in T‐B cell interactions because antibodies against other T cell surface antigens were inactive,e.g.those which remained in rabbit anti‐mouse thymocyte antiserum at a high titer after absorption with mouse brain tissue. Furthermore, the brain‐associated T cell antigen involved in the cellular interaction was differentiated from the Thy‐1 antigen by the failure of xeno‐anti‐Thy‐1.1 antisera to induce the interaction of B6.PL.Thy‐12T cells with B cells, and the presence of activity in rat anti‐AKR mouse brain serum which did not contain antibodies against Thy‐1.1 or Thy‐1.2 determinants.The data appear to support the hypothesis that the brain‐associated T cell antigen, as defined serologically in these studies, may represent a molecule which plays a role in the immunological