Studies in other species over 40 years ago demonstrated that chromosomes transmit hereditary characteristics, and that there is a constant number of chromosomes for each. Deviations from this number produced easily recognized abnormalities. The correct chromosome number of man was established only in 1956 as being 46 and aneuploidy reported only in 1959, first in mongolism and then in some sex anomalies. Trisomy for chromosome no. 12 in mongolism has been confirmed. In the sex anomalies, chromosome numbers of 47 with an XXY pattern in chromatin-positive Klinefelter''s syndrome and of 45 with an XO pattern in chromatin-negative Turner''s syndrome have also been established. Two patients with true hermaphroditism, having 46 chromosomes and an XX constitution as a basic pattern, are included as are reports on pseudohermaphroditism and leukemia. A new disorder which clinically resembles Klinefelter''s syndrome is reported. It differs, however, in that there are two sex chromatin masses in many intermitotic nuclei and that the diploid number is 48 with an XXXY complement. Non-disjunction, as shown by the work on Drosophila and other species, is the suggested mechanism for the production of aneuploidy in man.