The micronucleus frequency in cytokinesis-blocked lymphocytes of 152 females and 113 males aged between 20 and 89 years (minimum of 15 subjects per sex per decade) was compared. Marked differences in the micronucleus frequency of males and females were observed: (a) there was a greater dispersion in the results for females when compared to males in all age groups older than 40 years; (b) there was a significant positive correlation between micronucleus frequency and age in both sexes (p < 0.0001) but the slope of the linear regression line was steeper in females (slope = 0.499 micronuclei/year) compared to males (slope = 0.289 micronuclei/year) (p < 0.0045); (c) the micronucleus frequency in females (Mf) was significantly higher than the micronucleus frequency in males (Mm) in all decades examined (p < 0.05), the Mf,Mm ratio varied between 1.47 and 1.65 (mean +/- 1 SEM = 1.53 +/- 0.03) and showed no trend with age. These results suggest that an added mechanism, possibly the loss of X chromosomes, is contributing to the micronucleus frequency in females and highlights the importance of sex as a variable that has to be taken into consideration when interpreting data from cross-sectional studies utilising the cytokinesis-block micronucleus assay as a biomarker of chromosome damage.