The great strides made during the past two years in the whole field of mammalian cytogenetics have, in particular, enlarged our knowledge of the role of the mammalian sex chromosomes. The following summary briefly lists the most recent discoveries in the mouse, where genetic findings have played a relatively greater role than in the other species of mammals. The male-determining property of the mammalian Y chromosome, established earlier in mouse and man, has been further confirmed by the finding of an XXY mouse, which was detected by genetic means and has been studied cytologically. This animal is a fully viable, phenotypically normal, though sterile, male. Since various doubts concerning detectability of the XXY type have been removed by the discovery of this animal, it can be concluded that the occurrence of XXY in the mouse is extremely rare. It has been shown that the X chromosome of the mouse, when it is involved in certain chromosomal rearrangements, has the power to produce variegated-type position effects, a phenomenon formerly not observed in any animal except Drosophila. The fact that the X chromosome is involved in all four of the known cases of V-type position effect in the mouse indicates that it is strongly heterochromatic, while there may be little heterochromatin on the autosomes. Recent findings have shown that the presence of two X chromosomes is necessary for the expression of the position effect in one of them. This fact, when related to various cytological findings in other species, permits the hypothesis that, in mammals, genic balance requires the action of one X in a manner which precludes realization of its heterochromatic potentialities, so that only any additional X's present assume the properties characteristic of heterochromatin. A variety of different findings sheds light on the mechanisms that may lead to the occurrence of individuals with abnormal numbers of sex chromosomes. The XXY mouse proves, by virtue of its sex-linked marker genes, that nondisjunction can occur in the first meiotic division of a normal male (a proof not previously provided by human cases of XXY, which could have been of different origin). However, first-meiotic nondisjunction is apparently very rare in males, and there is not yet any evidence that it ever occurs in females. Data from numerous types of crosses involving five sex-linked markers yield the following results: no cases of X(M)X(M)Y or OX(P) have occurred to date; X(M)X(P)Y << X(M)O; OX(P) << X(M)O (where the superscripts M and P designate maternal and paternal derivation, respectively, of the X). The total frequency of XO individuals can be increased by irradiation shortly after fertilization. This treatment has yielded, in addition to X(M)O, several animals of the OX(P) constitution, a type that has not yet been found to occur spontaneously. The various findings on spontaneous and induced frequencies of mice with abnormal numbers of sex chromosomes lead to the conclusion that XO individuals are most often the result of events occurring after fertilization. Specifically, it is suggested that there exists a relatively high probability of loss of the paternally contributed sex chromosome some time between fertilization and the first cleavage(32).