The CD4 T-lymphocyte differentiation antigen is an essential component of the cell surface receptor for human immunodeficiency viruses (HIVs) causing AIDS (acquired immune deficiency syndrome) (refs 1-3). Peripheral blood lymphocytes of apes, New World and Old World monkeys express cell surface antigens homologous to CD4 of human T-helper lymphocytes. The cells of several of these species can be infected in short term culture with diverse strains of the type-1 or type-2 human immunodeficiency viruses (HIV-1 and HIV-2). HIV-1 is the prototype AIDS virus, and HIV-2 is the second type of AIDS virus, prevalent in West Africa. Infection of the primate cells correlates with evolutionary conservation on CD4 of one particular epitope cluster, and is inhibited by treatment of the cells with monoclonal antibodies to this epitope. The capacity of HIV to replicate in simian cells may provide a means for evaluating antiviral drugs and vaccines.