The endogenous free radical, nitric oxide (NO), plays a neurotransmitter-like role in vascular endothelium, a second-messenger role in N-methyl-D-aspartate (NMDA)-responsive neurons in the central nervous system (CNS), a neurotoxic role after its release from these neurons, and a cytotoxic role after its release by macrophages. NO also derives from exogenous sources, such as the nitrite inhalants, amyl, butyl and isobutyl nitrite. There is evidence that abuse of nitrite inhalants can affect immunomodulation, and epidemiological studies suggest that such abuse may be a cofactor in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Hitherto, however, the potential role of NO in such pathogenesis has not been examined. This paper presents some current evidence that implicates both endogenous and exogenous sources of NO in AIDS and associated pathology.