Infectious retrovirus(es) associated with the human (LAV, HTLV-III, ARV) and simian (SAIDS-1) acquired immune deficiency syndrome were compared by electron microscopy, immunofluorescence and immunoblotting techniques and by restriction endonuclease mapping of the viral genomes. The extracellular virus particles had similar type D morphology, but intracytoplasmic type A nucleoids were found only in SAIDS virus infected cells. Although the antigens of the three prototype AIDS viruses were similar, no cross-reactivity with the SAIDS virus was detected. Molecular hybridization and restriction enzyme analysis also revealed that the SAIDS and AIDS viruses were genetically unrelated. However, only minor differences, consistent with strain polymorphism, were found between the three AIDS virus isolates. Thus, the retroviruses associated with AIDS in macaques and humans are unique to each species.