We recently reported the isolation of a novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously named LAV-2), from patients with acquired immune deficiency syndrome (AIDS) originating from West Africa. This virus is related to HIV-1, the causative agent of the AIDS epidemic now spreading in Central and East Africa, as well as the USA and Europe (see ref. 3 for review) both by its morphology and by its tropism and in vitro cytopathic effect on CD4 (T4) positive cell lines and lymphocytes. But preliminary hybridization experiments indicated that there are substantiated differences between the sequences of the two genomes. Furthermore, the proteins of HIV-1 and HIV-2 have different sizes and their serological cross-reactivity is restricted to the major core protein, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1-positive sera. We now report the molecular cloning of the complete 9.5-kilobase (kb) genome of HIV-2, the observation of restriction site polymorphism between different isolates, and a preliminary analysis of the relationship of HIV-2 with other human and simian retroviruses.