A bidirectional circuit exists between the central nervous system and the immune system, since activation of the immune system results in the elaboration of cytokines and inflammatory mediators; these mediators induce hypothalamic CRF, which stimulates the release of the same immunosuppressive molecules that mediate the response to stress. The brain, therefore, is likely to be involved in immune system regulation. Hypofunctioning of the HPA axis with insufficient down regulation may be involved in autoimmune or other diseases with excessive immune system activation. Hyperfunctioning of the HPA axis, which is not appropriately suppressed, has been found in a large number of patients with major depression. Evidence that stress is an important factor in both lowering resistance to infectious agents and contributing to the reactivation of latent viruses is discussed. Also discussed is the evidence that stress induces proinflammatory cytokines which may contribute to both the pathogenesis of inflammatory diseases of unknown etiology and the progression of HIV infection to AIDS by activation of HIV replication.