The study of AIDS has contributed substantially to a growing awareness of the relationship between the immune and nervous systems. This chapter discusses a comparison of the impairments in the nervous and immune systems that arise from HIV infection. The chapter also emphasizes the examination of the evidence for the role of the major envelope glycoprotein of HIV—gp120—as a causative agent for the pathology of AIDS, which may occur as the result of an interference with neuroimmune effectors. The latter idea serves to highlight the thesis that the nervous and immune systems share many common chemical mediators. Although the identity and action of these substances are uncertain, interference in their action may contribute to, if not define, the development and course of AIDS. The chapter focuses on the identification of such substances as well as possible roles for peptides as protective agents against the deleterious effects of HIV in the nervous system.