To date, very little is known concerning the clinical spectrum of human immunodeficiency virus type 2 (HIV-2) infection, and the question as to whether HIV-2 will ultimately prove to be as pathogenic as human immunodeficiency virus type I (HIV-1) remains, as yet, unanswered. We reviewed the currently available reports of HIV-2 infection to assess what is known about the extent of HIV-2 pathogenicity as it compares to HIV-1 pathogenicity. There is evidence that HIV-2 is associated with AIDS. Most of this evidence, however, comes from descriptive case-report type data that do not meet the basic requirements for defining causality. The most significant problems are the lack of control groups and the absence of a documented temporal relationship with HIV-2 infection preceding the development of AIDS. Comparisons of the epidemiology and disease association between HIV-1 and HIV-2 in Africa may suggest relative pathogenic effects. Although certain comparisons between HIV-2 and HIV-1 are difficult to make, we conclude on the basis of existing data that the pathogenic effects and the natural history of HIV-2 are distinct from those of HIV-1.