The author presents the case history of the first patient with HIV-I group O reported in the United States. The various human retroviruses and their clinical syndromes are described and the increasing diversity of HIV-1 strains and their spread are documented. The discovery of the divergent group O and its spread from endemic areas are discussed. The clinician is alerted to the pitfalls of laboratory diagnosis and is advised to seek special studies when clinical findings and epidemiologic history suggest the possibility of HIV infection.