The immunopathologic reaction of rabies virus infection is manifested by early death in the presence of exogenous or endogenous antibody. Two hypotheses will be tested: antibody of a given specificity, affinity and avidity kills rabies-infected mice directly; or antibody promotes killing of virus-infected animals indirectly by binding to target cells or to effector cells. In cytotoxicity assays, suppressor T cells will be isolated by use of monoclonal antibody directed toward specific surface glycoproteins. The relationship of antigen binding to T cell receptors and the generation of suppressor T cells will be determined. The potential role of killer T cells in altering the pathogenesis of rabies virus will be determined by in vitro and in vivo tests. The regulatory effects of suppressor T cells on killer T cell activity will be determined in vivo. Finally, we will determine quantitatively the ratio of defective-interfering to standard particles in virus inocula which show either immunopathologic disease or increased virulence after cytoxan treatment.