Peripheral blood leukocytes isolated from men and women were studied for their capacity to metabolize estrone (E1) sulfate. Fresh human leukocytes (granulocytes and mononuclear cells) were incubated in phosphate buffer, pH 7.4, containing [3H]E1S for 1 h at 37 C. The samples were extracted with chloroform for measurement of the [3H]E1 formed, and the results were corrected for nonenzymatic hydrolysis. The mean E1 sulfatase activity in leukocytes isolated from normal women in the follicular phase of their cycle was 75% higher than that during the luteal [1840 +/- 179 (+/- SE) vs. 1048 +/- 101 fmol E1 micrograms protein-1 h-1; P less than 0.004] and higher than that in normal men (875 +/- 123; P less than 0.002), but was not different from that in menopausal (1349 +/- 151) or hirsute women (1700 +/- 222). In pregnant women, the mean leukocyte E1 sulfatase activity was significantly lower (861 +/- 147) than that in nonpregnant women in the follicular phase (P less than 0.003). These results suggest that progesterone may modulate E1 sulfatase activity, whereas estrogens do not.