The metabolic clearance rate (MCR) of progesterone was studied by the single intravenous injection method (10,11) in pregnant rats, pseudopregnant rats with or without deciduomata and ovariectomized rats. The disappearance of progesterone from peripheral serum apparently followed a double exponential curve. The MCR was analyzed, therefore, in terms of a two-compartment model and was found to be similar in all conditions examined. The mean MCR during pregnancy, calculated from values obtained on days 4, 8, 10, 12, 15, and 21, was 32.79 ± 2.71 I/day. A similar value was obtained for days 6 and 10 of ordinary pseudopregnancy (29.91 ± 2.17 I/day), on days 10 and 16 of pseudopregnancy in deciduomabearing rats (38.19 ± 4.19 I/day), and 6 days after ovariectomy of cyclic rats (25.53 ± 0.30 I/day). Production rates of progesterone (MCR × peripheral serum concentration) were: pregnant, day 10: 2.13 mg/day; day 15: 4.55 mg/day; deciduoma-bearing pseudopregnant, day 10: 2.86 mg/day; day 16: 1.37 mg/day; ordinary pseudopregnant, day 10: 1.59 mg/day. These data confirm previous findings of an increased production rate of progesterone during pregnancy but indicate that the calculated production rate is much higher than that obtained by measurement of progesterone in the ovarian vein effluent (14,15,16). (Endocrinology93: 1200, 1973)