For many years, ageing of gametes as a result of prolonged retention in the female reproductive tract before fertilisation has been circumstantially associated with major birth defects. To assess this association, we studied pregnant women who had recorded the timing, with regard to presumed ovulation, of the coital event leading to conception. We found major anomalies in 11 (2.7%) of 400 infants born to women with optimally timed conceptions (on the day of or 1 day before ovulation), compared with 14 (2.5%) of 538 infants of women with non-optimally timed conceptions (odds ratio 0.94, 95% CI 0.43-2.06). The numbers of infants with Down's syndrome were two (0.5%) of 400, and four (0.7%) of 538, respectively (1.48, 0.27-8.06). There is no association between ageing gametes and major birth defects, including Down's syndrome.