Black women with endometrial cancer have more advanced disease and less favorable tumor grade than do white women. This study evaluated whether racial differences in tumor grade could be explained by hormone-related factors and other putative determinants of grade. Subjects included 207 white and 81 black postmenopausal women diagnosed with primary cancer of the uterine corpus between 1985 and 1987. Blacks had poorer tumor grade than whites (odds ratio for FIGO grade 2 versus grade 1 is 1.8; odds ratio for grade 3 versus grade 1 is 2.8). Over 75% of the excess of poorly differentiated tumors versus well-differentiated tumors among blacks could be explained by racial differences in use of replacement estrogens, age at first pregnancy, history of oophorectomy, poverty, stage of disease, use of screening, and access to health care. The most prominent factor was estrogen therapy, which was associated with favorable tumor grade and was used much less frequently by blacks. Although not statistically significant, a moderate racial difference in tumor grade remained after control of the potential explanatory explanatory variables. This may reflect true biologic variation between blacks and whites and may explain, in part, the observation that blacks with endometrial cancer have a worse prognosis.