To explore the influence of sex on sister chromatid exchange (SCE) level, a pair of chimeric twins was examined for differences in SCE frequency between the XX and XY cells present in each individual. By this method, the influence of possible differences in environmental exposure was eliminated. SCE levels were varied by growing the cells in media containing 0, 1.3 X 10(-7), or 6.5 X 10(-7) M melphalan. XX cells showed a higher SCE count than XY cells. This difference increased with increasing SCE level and ranged from 5.4% to 7.8% (P = 0.0003) of the SCE counts. Only about 2% of the difference could be explained by the higher amount of DNA present in the XX cells than in the XY cells. In this case XX cells seemed to be more sensitive to SCE-inducing agents than XY cells.