Melatonin has a variety of functions in human physiology and is involved in a number of pathological events including neoplastic processes. The tissue protective actions of melatonin are attributed to its antioxidant activity though, under certain conditions, melatonin might also exert oxidant effects, particularly in cancer cells. This study evaluated the effects of 10(-5) and 10(-3) m concentrations of melatonin on human leukemia cells. Moderate cytotoxic effects of melatonin at 10(-3) m concentrations were observed in CMK, Jurkat and MOLT-4 cells which was associated with significant reactive oxygen species (ROS) generation. Melatonin treatment was not associated with significant cytotoxicity in HL-60 cells, although the generation of ROS was significantly increased. K562 and Daudi cells did not appear to be effected by melatonin treatment. Cellular membrane lipid peroxidation was not influenced by melatonin with the exception of CMK cells. Cell cycle kinetics were not affected in melatonin-treated samples, again with the exception of CMK cells which showed increased apoptosis. Melatonin, therefore, induces the production of ROS that may be associated with cytotoxicity depending on the concentration of melatonin in some leukemia cells and does not appear to stimulate leukemia cell growth. These pro-oxidant actions of melatonin may assist in limiting leukemic cell growth.