Thirty-five consecutive patients with adenocarcinoma of the endometrium and an equal number of control subjects matched to the cancer patients for age and percentage of ideal weight were studied prospectively. In the cancer patients, the mean +/- SE serum androstenedione, testosterone, estrone (E1) and estradiol (E2) levels were 503 +/- 34 pg/ml, 224 +/- 22 pg/ml, 38.7 +/- 3.6 pg/ml, and 14.5 +/- 0.9 pg/ml, respectively. Similar concentrations were found in the control subjects. Body weight and percentage of ideal weight showed highly significant correlations (P less than 0.001) with E1 and E2 but not with the androgen concentrations in either group. The heavier patients had higher E1 and E2 levels. Age and years since menopause did not correlate with any of the hormonal levels. The cancer patients with overt diabetes tended to be more obese and have higher estrogen levels than did the nondiabetic subjects. Those with a history of prior estrogen usage were more slender and had lower endogenous estrogens than the nonusers. Twenty-three of the cancer patients (66%) had a presumed risk factor(s) for the development of this tumor, that is, excess body weight, high endogenous estrogen levels, or a history of prior estrogen usage. These data support the concept that conditions which lead to continued, unopposed estrogen stimulation may be associated with malignant transformation of the endometrium.