The effector function of CD8+ lymphocytes depends on recognition by the TcR-CD3 complex of an oligopeptide presented by an MHC class I molecule on target cells. Recently it has been shown that MHC class I molecules change their conformation upon depolarization of human B lymphoblastoid JY cells. We studied here the effects of changes in membrane potential of target cells on the function of cytotoxic T lymphocytes (CTL). Selective alterations of plasma membrane potential of JY target cells were achieved by treatments with specific ionophore molecules as well as with Na(+)-K(+)-ATPase inhibitor, while the cytotoxic lymphocytes were not influenced. The plasma membrane was depolarized by gramicidin D and ouabain, while hyperpolarization was induced by valinomycin treatment. Alterations of the resting membrane potential of target cells in both direction resulted in an enhanced cytotoxic activity. The observed changes in cytolytic activities of cytotoxic T effectors may have a more general biological significance, namely apoptotic cells become depolarized after a given time, moreover neoplastic and virus infected cells also frequently show decreased membrane potential. A more efficient recognition of these cells by CTL is supposed to enhance the efficiency of their elimination, as well.