The effect of progesterone (P) on peripheral estrone sulfate (E1S) was investigated in postmenopausal women using E1S constant infusions. The metabolic clearance rate of E1S (MCRE1S) was significantly lowered by P administration (p less than 0.01), while no significant changes were observed for E1S----E1 conversion ratio. The present findings suggest that P can affect the E1S peripheral fate inducing deep changes in estrogen equilibrium.