This chapter reviews several studies that detail the in vivo effects of gamma interferon in monocyte activation, and which provide a basis for studying the effects of interferon gamma in acquired immunodeficiency syndrome (AIDS) patients. Immunologic perturbations associated with human immunodeficiency virus (HIV) infection have been documented since the recognition of the AIDS in 1981. The prevalence and the severity of these abnormalities vary with the clinical stages of HIV infection. Asymptomatic HIV-infected persons have relatively intact host defenses but, as their disease progresses to generalized lymphadenopathy, the AIDS-related complex, and ultimately AIDS, they acquire more generalized and profound immune dysfunction. Experiments conducted in the 1960s and 1970s demonstrated that human peripheral-blood mononuclear cells release interferon gamma into culture supernatant, and that these crude lymphocyte supernatants contained factors which were able to modulate macrophage function, resulting in enhanced antimicrobial effects.