Previous reports demonstrated that alloantigen- or xenoantigen-specific antibodies displayed neutralizing activity toward human or simian immunodeficiency viruses, In the present article we have addressed the question of alloantigen-induced cell-mediated anti-HIV activity, We show that allostimulation resulted in a lymphocyte population (largely of the CDS-positive phenotype) with the capacity to inhibit HIV-1 replication in PHA blasts of homologous and, unexpectedly, also autologous origin, The allostimulated effector cells exerted their activity via a noncytolytic mechanism: Experiments in which direct cell-to-cell contact between allostimulated effecters and HIV-1-infected PHA blasts was prevented by a semipermeable membrane indicated that soluble mediators were involved in inhibition of HIV-1 replication, As such allostimulated effecters not only would have the capacity to prevent viral replication in allogeneic HIV-l-infected cells (known to play an important role in HIV-1 transmission in vivo), but also might inhibit HIV-1 growth in autologous lymphocytes, the concept of an AIDS vaccine containing both HIV-1 antigens and alloantigens warrants further consideration.