In a series of 156 females and 149 males with a Down syndrome (DS) child, a case-control study was performed to evaluate the effect of abdominal-pelvic exposure to diagnostic x-rays prior to conception on nondisjunction (ND). Cytogenetic analysis using QFQ banding allowed unequivocal identification of ND parents as cases. Partners of ND parents were treated as control group. Odds ratio for the association of x-rays exposure and ND occurrence (stratified for sex and age) was 1.85 (borderline to significance: with a 95% confidence interval 1-3.44). Such an association appeared highly significant in older fathers and borderline to significant in younger mothers, when age groups were analyzed separately. By comparing mean parental ages at birth of the propositus, the prevalence of exposure to x-rays appeared moderately associated with aging in control parents of both sexes. Furthermore, the mean age of unexposed ND parents of paternally derived SD cases was the same as the referent population's, suggesting that age is not a risk factor for ND in the male, except for being associated with increasing exposure risk. Conversely, risk attributable to x-rays exposure in the female appears to be progressively diluted with increasing age, by strongly age-dependent high risk, presumably due to biologic factors that are not affected by environmental exposure.