We have developed a series of murine monoclonal antibodies to guinea pig T lymphocytes and accessary cells and used these antibodies as tools to further our understanding of the process of T cell activation by both non-specific and specific immunologic stimuli. Our studies have been concentrated in several different areas. We have 1) developed a monoclonal reagent to a cell surface antigen distinct from the receptor for the T cell growth hormone, interleukin-2 (IL-Z), which plays a critical role in the activation signal transmitted by IL-2 to the T cell; 2) employed the immunosuppressive drug, cyclosporin A (CY A), as a probe for T cell activation and demonstrated that CY A inhibits both IL-2 production as well as IL-2 receptor induction; 3) analyzed the immunologic makeup of the central nervous system infiltrate in both acute and chronic experimental allergic encephalomyelitis (EAE); 4) identified monoclonal antibodies to human Ia antigens which cross react with guinea pig Ia and which recognize evolutionary conserved epitopes which play unique roles in T cell activation.