In an attempt to determine a normal level of CA125 in postmenopausal women, CA125 levels of normal postmenopausal women (n = 36, 58.2 +/- 8.1 years) and postmenopausal women undergoing hormone replacement therapy (HRT) (n = 111, 56.8 +/- 6.1 years) were studied. A mean CA125 concentration of 10.0 +/- 3.8 U/ml was found in postmenopausal women without HRT and was significantly lower than that of postmenopausal women undergoing HRT (12.8 +/- 3.8 U/ml), indicating that the cutoff level of CA125 in postmenopausal women or women without reproductive organs should be estimated at a level lower than that conventionally accepted. A receiver operating characteristic (ROC) curve for a preoperative evaluation of myometrial invasion was analyzed in postmenopausal women with endometrial cancer (n = 110). A novel cutoff level of 20 U/ml of CA125 could detect myometrial invasion to more than one-half of the myometrium with sensitivity of 69.0%, specificity of 74.1%, positive predictive value of 58.8%, and negative predictive value of 81.6%. In addition, the distribution of CA125 levels was analyzed in patients who had undergone an operation for endometrial cancer more than 2 years earlier and as yet had no clinical evidence of recurrence of the disease. Ninety-six point two percent of 619 measurement values were lower than 20 U/ml. These results suggest that the novel CA125 level of 20 U/ml is clinically useful for preoperative evaluation and postoperative surveillance of endometrial carcinoma.