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Studies on the metabolism of progesterone in rabbit plasma and tissues during constant infusion of [³H]progesterone revealed a gradual increase in the concentration of progesterone in plasma until a state of equilibrium was attained about 2 h after the start of infusion. The metabolic clearance rate of progesterone was 0·116 l/min and the turn-over time was 0·006 min/ml plasma. Under conditions of equilibrium, the concentration of radioactivity as well as that of labelled progesterone was higher in the tissues than in plasma. On a unit–weight basis, myometrium localized 6·6 nCi, Fallopian tube 5·5 nCi and vagina 6·1 nCi [³H]progesterone/g tissue. A higher concentration of progesterone, 16·5 nCi, was localized in the mammary gland tissue. Skin localized only 0·9 nCi progesterone and the lowest amount (0·34 nCi/ml) was found in plasma.

The metabolism of progesterone in tissues differed from that in plasma. In plasma only 5·6% of the infused steroid was recovered as unconverted progesterone and the major amount was metabolized to polar compounds with smaller amounts of 5-pregnane-3,20-dione, 5-pregnan-3β-ol-20-one and 20-hydroxypregn-4-en-3-one. In the myometrium and Fallopian tubes the major metabolites were 5-pregnan-3β-ol-20-one and 5-pregnane-3,20-dione respectively. In the vagina, like the myometrium, 5-pregnan-3β-ol,20-one was the major metabolite. 20-Hydroxypregn-4-en-3-one was the major identified metabolite of mammary gland tissue.