1. The material included in this paper consists of F1 and F2 virgin female mice derived from a cross between a strain high in mammary cancer incidence (dilute brown) and one relatively low in incidence of mammary cancer but relatively high in the incidence of various internal tumors (yellow).
2. In the F1 and F2 hybrid generations the yellow animals have a significantly lower incidence of mammary tumors than do the non-yellows. This is the first clear case of a difference in the incidence of spontaneous tumors in mice associated with a color difference.
3. Mammary tumors occur, however, significantly earlier in the yellow mice and are just as malignant as those appearing in the non-yellows.
4. The incidence of tumors other than mammary is not significantly different in the yellow and non-yellow hybrids. Such tumors, however, occur distinctly later in life than do the mammary tumors. This provides additional evidence that, in mice, mammary tumors cannot be considered to be the same biological phenomenon as are other types of tumor.
5. A study of the physiology of reproduction of yellow and non-yellow mice within the yellow stock suggests that the yellows pass through their reproductive cycle earlier than do the non-yellows. The duration of the cycle in the two forms is essentially equal. This fact would satisfactorily explain the earlier incidence of mammary tumors in yellow mice.
6. The lower incidence of mammary tumors in yellows as compared with non-yellows may be at least in part due to the same phenomenon. This would follow because the opportunity for mammary tissue in yellow mice of cancer age to be continuously affected by ovarian secretion would be less than in non-yellows. This would result in a higher percentage of yellows reaching an age at which stimuli from the ovary ceased before the mammary tissue had reached an age at which tumor formation is most frequent.
7. There is some evidence that, in this cross, dilute (dbdb) mice are less apt to form mammary tumors than are intensely pigmented animals. This point, however, needs further investigation before it can be considered to be established.
8. The facts recorded in this paper demonstrate that not all forms of tumor or all colors of mice can be lumped together in studying either the physiology or genetics of spontaneous tumor incidence.