Human peripheral blood T lymphocytes are readily transformed to continuous growth by Herpesvirus saimiri subgroup C strains. The immortalized cells express the phenotype of mature activated T cells and bear either CD4 or CD8 surface markers. Here we report that Herpesvirus saimiri transformed CD4+ cell lines are highly susceptible to infection with human immunodeficiency viruses types 1 and 2. The prototype viruses HIV-1IIIB and HIV-2ROD replicated rapidly and caused cell death within 14 days. These cell lines did also support growth of a poorly replicating HIV-2 strain (HIV-2NEP) and of primary clinical isolates. Thus H. saimiri transformed T cells represent a new system for HIV propagation and isolation, especially for HIV-2 strains with restricted cell tropism. These cells should be considered as an alternative approach in cases where conventional attempts fail.