The influence of diethylstilbestrol (DES) on the SCE frequency was studied in various cell systems (V79, HTC, DON, WI-38, human lymphocytes) differing in their ability to metabolize the two promutagens benzo(a)pyrene and cyclophosphamide as well as after incubation with exogenous metabolic systems (S9 mix and peroxidase/H2O2) and in vivo on cells from the bone marrow of the Chinese hamster. DES concentrations from 10(-6) to 10(-4) M were tested. Slight SCE induction was observed only at the highest concentration (10(-4) M) of DES in human lymphocytes treated with DES for the entire culture period of 72 h and in DON cells. No increase of the SCE rate was determined in the other cell lines and in vivo. The combination with S9 mix or peroxidase/H2O2 also had no influence on the SCE frequency. These findings cast doubt on the assumption that DES is metabolized to a DNA-damaging compound subsequently leading to SCE induction. The positive findings in the SCE test are more likely to be products of an indirect and rather unspecific effect.