It has been known for some time that there is an association between chronological aging and X-chromosome aneuploidy in peripheral blood lymphocyte cultures from females. In an attempt to elucidate the mechanism of X-chromosome aneuploidy in aging females, we used a BrdU late-labeling technique to determine the X-inactivation pattern in 45, X and 47, XXX lymphocytes of older women. In 50 of 58 X-aneuploid cells the inactive X chromosome was missing or extra. This implies that either the inactive X has a special propensity for mitotic errors or mitotic errors occur at random but subsequent selection is less stringent against cells with a missing or additional inactive X chromosome than against aneuploid cells involving the active X chromosome. Evidence is presented in favor of the former hypothesis.