Cells in human peripheral blood were treated in vitro with increasing concentrations of melatonin (0.5 or 1.0 or 2.0 mM) for 20 min at 37 +/- 1 degrees C and then exposed to 150 cGy gamma-radiation from a 137Cs source. The lymphocytes which were pre-treated with melatonin exhibited a significant and concentration-dependent decrease in the frequency of radiation-induced chromosome damage as compared with the irradiated cells which did not receive the pre-treatment. The extent of the reduction in radiation-induced chromosome damage observed with 2.0 mM melatonin was similar to that found in lymphocytes pre-treated with 1.0 M dimethyl sulfoxide, a known free radical scavenger. Melatonin at 2.0 mM (a 500 x lower concentration) was as effective in decreasing the radiation-induced chromosome damage as dimethyl sulfoxide at 1.0 M. These observations may have implications for human protection against damage due to endogenously produced free radicals and also due to exposure to free radical producing physical and chemical mutagens and carcinogens.