We investigated the activity of estrone sulfatase in normal and pathological endometrium. In normal endometrium, the estrone sulfatase activity [pmol E1 X min-1 X (mg prot)-1] was 23.13 +/- 8.44 (mean +/- SD). An increase (p less than 0.01) of estrone sulfatase activity (62.81 +/- 21.97) was noted in mild endometrial hyperplasia. In focal hyperplasia (when the measurements were performed in the normal endometrial biopsies) such an increase was not noted (19.10 +/- 5.33). Estrone sulfatase activities of moderate hyperplasia (25.30 +/- 11.40) and endometrial neoplasia (30.30 +/- 9.57) were in the same range as in normal endometrium. Treatment with progestagen simultaneously reduced hyperplasia and estrone sulfatase activity. But when morphologically abnormal endometrium persisted after treatment, estrone sulfatase activity remained increased. The increase of estrone sulfatase activity appeared to be specific to mild endometrial hyperplasia. The role of estrone sulfatase in the pathogenesis of endometrial hyperplasia is discussed.