This paper defines potential peptide cross-reactivity between HIV-1 and the human host. Specifically, the amino acid primary sequence of HIV-1, isolate CDC-451, was analyzed for potential immunopathological relationships with the human proteome. The results revealed that: 1) HIV-1 shares 50 heptapeptides and three octapeptides with the human proteome; 2) 34 of the 50 shared heptapeptides are experimentally validated epitopes targeted by immune responses following HIV-1 infection; 3) the viral heptapeptide epitopes are present in human proteins that, when altered, are associated with disease characteristics of acquired immunodeficiency syndrome (AIDS) such as CD4+ cell loss, encephalopathy, schizophrenia, myopathy, cardiovascular disorders, hypertension, corneal diseases, diarrhea, lymphoma, and bladder cancer; 4) at the pentapeptide level, the viral-versus-human overlap is extensive (14,227 matches), with the viral pentapeptides disseminated throughout 10,312 human proteins. The findings are discussed in relationship to HIV-1 escape from immune surveillance, adjuvant-induced HIV-1 immunogenicity, autoimmune cross-reactions following human hyperimmune responses against HIV-1, and AIDS.