MacDowell and Richter found that the incidence of leukemia in hybrids could be roughly correlated with the total heredity from the high leukemia C58 strain when C58 mice were crossed with low leukemia StoLi animals. A “maternal influence” was suggested, for if the female parent was of the C58 strain the incidence of leukemia was greater than in the reciprocal cross. Cole and Furth, working with the Ak and Rf stocks, concluded that susceptibility to leukemia is probably inherited as a multiple factor character, and is influenced by undetermined environmental factors. In various crosses the common logarithm of the percent leukemia was a simple function of the percent heredity from the high leukemia stock. Female mice had a higher incidence of leukemia than males. It was concluded that the genetic basis for spontaneous leukemia may vary for different stocks of mice, since Mercier had observed that susceptibility to spontaneous lymphosarcoma was inherited as a simple Mendelian recessive character, and the results of MacDowell and Richter were somewhat at variance with those of Cole and Furth. In later experiments with the Ak stock Furth, Boon, and Kaliss found that when animals of this stock were crossed with the C3H rather than the Rf stock the incidence of leukemia in F1 hybrids was higher, approximating that in the Ak stock, if the female parent was of the latter stock (50 as compared with 58%); the incidence of leukemia was 34% in F1 hybrids of the reciprocal cross. The present study was carried out using the F strain of mice as the high leukemia stock. Of 325 control animals there were 173 cases of leukemia, or an incidence of 53%.