The aim of this study was to assess radioprotective effects of quercetin and the ethanolic extract of propolis (EEP) in CBA mice exposed to a single radiation dose 4 Gy (60Co). The mice were treated with 100 mg kg(-1) quercetin or EEP a day for three consecutive days either before (pre-treatment) or after gamma-irradiation (therapy). Leukocyte count was determined in blood drawn from the tail vein, and DNA damage in leukocytes was assessed using the alkaline comet assay. Genotoxic effects of the test compounds were also evaluated in non-irradiated mice. The levels of radioprotection provided by both test compounds were compared with those established in mice that were given chemical radioprotector S-(2-aminoethy1)isothiouronium bromide hydrobromide (AET). Mice that received pre-treatment were less sensitive to irradiation. Mice given the post-irradiation therapy showed a slight but not significant increase in total leukocyte count over irradiated negative control. Quercetin showed better protective properties than EEP in both pre-treatment and therapy, and activated a higher number of leukocytes in non-irradiated mice. The alkaline comet assay suggests that both natural compounds, especially when given as pre-treatment, protect against primary leukocyte DNA damage in mice. At tested concentrations, EEP and quercetin were not genotoxic to non-irradiated mice. AET, however, caused a slight but not significant increase in DNA damage. Although the results of this study show the radioprotective potential of the test compounds, further investigation is needed to clarify the underlying protection mechanisms.