Millimolar concentrations of sodium ascorbate (vitamin C) induced apoptotic cell death in human promyelocytic leukemic HL-60 cells. The apoptotic cells displayed a smaller cell volume, disappearance of cell surface microvilli, appearance of cytoplasmic vacuoles, chromatin condensation, nuclear fragmentation and production of apoptotic bodies. The apoptosis-inducing activity of sodium ascorbate was significantly enhanced by noncytotoxic concentrations of CuCl2, but was almost completely eliminated by FeCl3. CuCl2 transiently stimulated the hydrogen peroxide (H2O2) production by sodium ascorbate, whereas FeCl3 slightly reduced the H2O2 production. alpha-Tocopherol (vitamin E) slightly enhanced the radical and H2O2 productions, and apoptosis induction by sodium ascorbate. The effect of alpha-tocopherol seems to be rather specific for ascorbic acid, since alpha-tocopherol did not significantly affect the cytotoxic activity of CuCl2, FeCl3 nor gallic acid. The present study demonstrated the cooperative action of vitamins C and E.