A NUMBER of murine T-cell hybridomas undergo apoptosis within a few hours of activation by specific antigens, mitogens, antibodies against the T-cell antigen receptor, or a combination of phorbol ester and calcium ionophore(1-3). This phenomenon has been extensively studied as a model for cional deletion in the immune system, in which potentially autoreactive T cells eliminate themselves by apoptosis after activation, either in the thymus(4) or in the periphery(5). Here we show that the Fas/CD95 receptor, which can transduce a potent apoptotic signal when ligated(6,7), is rapidly expressed following activation of T-cell hybridomas, as is its functional, membrane-bound ligands, Interference with the ensuing Fas/Fas-ligand interaction inhibits activation-induced apoptosis, Because T-cell receptor ligation can induce apoptosis in a single T hybridoma cell, we suggest that the Fas/Fas-ligand interaction can induce cell death in a cell-autonomous manner.