Sufficient evidence of a correlation between infrequent coitus and Down syndrome (DS) has now accumulated to warrant reevaluation of the suggested biological mechanisms. The evidence provides no support for delayed fertilization as the mechanism responsible for this correlation, as was originally proposed by German [Nature 217:516-519, 1968]. A better explanation of this association is provided by the sperm aging hypothesis, which gains its support from both animal studies and chromosomal findings of a paternal contribution to DS. The animal studies supporting this hypothesis show an increased incidence of sperm-derived trisomies resulting from sperm stored for prolonged periods in the male tract. The chromosomal findings show a paternal origin in 20% of DS infants; the sperm aging hypothesis concerns the biological mechanism in this 20%. In addition to explaining the excess of DS for older mothers, the sperm aging hypothesis explains the excess for teenage unwed mothers and indicates that sperm aging from decreased ejaculatory frequency may be a cause of DS in all age groups. Testable directly in humans against German's delayed fertilization hypothesis, the sperm aging hypothesis has immediate clinical implications. It suggests 1) an approach to reduce the incidence of DS and miscarriages and 2) clinical research that will increase knowledge of the circumstances indicating a need for antenatal monitoring.