The origin of the supernumetary chromosome 21 in Down's syndrome was traced by the use of polymorphic regions of this chromosome. The present results interpretated in the light of the extensive literature may be summarized as follows; 1. The meiotic error involved in trisomy 21 can take place in both sexes and occurs at random. It occurs twice as frequently in the female than in the male. This situation is paralleled by the 2:1 ratio found in XXY-syndrome concerning the supernumerary X. 2. In both sexes non-disjunction occurred twice as frequently in the first than in the second meiotic division. 3. The rate of meiotic errors is largely dependent on age. The present study confirms the increase in meiotic errors with age of mother; moreover, increasing age of the father seems to enhance non-disjunction in spermatogenesis. Trisomy 21 on the basis of sporadic translocation in the child seems to be independent of the parental age. The present study includes two cases of translocation 21/21. In both cases the errors took place in mothers aged 18 and 19, respectively. 4. A new finding consists in the observation that previous pregnancies and deliveries may influence errors in oogenesis. In cases of maternal origin significantly more previous pregnancies and deliveries were found than in cases of trisomy of paternal origin. 5. A study of quinacrine polymorphism of chromosome numbers 1, 3, 9, 13, 14, 15, 16, 21, 22 and Y showed no significant difference between parents of children with Down's syndrome and controls. Moreover, the parents in whom the non-disjunction exists in parents of trisomic children, it cannot be detected by such methods. Recent observations made in the course of prenatal diagnosis contradict such an individual predisposition. The present results, after confirmation and augmentation, especially by implementation of biochemical methods, should prove of importance in genetic counseling and as guidelines in the indications for prenatal diagnosis.