The objective of this study was to examine the potential radioprotective properties of pharmacological doses of melatonin in whole-body irradiated mice. CD2-F1 male mice were treated with melatonin, a secretory product of the pineal gland, and then whole-body irradiated with an acute dose (150 cGy) of 137Cs gamma rays. Peripheral blood and bone marrow cells were examined for genetic damage, which was determined by comparing the incidence of micronuclei (MN) in both melatonin pre-treated and non-treated irradiated animals (and control mice). The percentages of polychromatic erythrocytes (PCEs) in unirradiated mice ranged between 3.1 +/- 0.23 and 3.2 +/- 0.19 in the peripheral blood and between 51.0 +/- 2.03 and 52.8 +/- 2.00 in the bone marrow. Whole-body irradiation resulted in a significant decrease in the percentages of PCEs in the peripheral blood and bone marrow cells. In both tissues, irradiated mice that were pre-treated with melatonin (5 or 10 mg/kg) exhibited a dose-dependent increase in the observed incidence of PCEs relative to the expected incidence. The incidence of MN in unirradiated mice ranged between 4.2 +/- 0.92 and 4.6 +/- 0.97 in the peripheral blood and between 5.0 +/- 1.05 and 5.5 +/- 1.08 in the bone marrow. Whole-body irradiation resulted in a significant increase in the incidence of MN in both tissues. In both tissues, irradiated mice that were pre-treated with melatonin exhibited a significant and dose-dependent reduction in the observed incidence of MN (relative to the expected incidence). Under the experimental conditions tested, the data indicate that melatonin has the ability to protect the genetic material of hematopoietic cells of mice from the damaging effects of acute whole-body irradiation.