Progesterone-4-14C was found to be actively metabolized by minces of human skin and vaginal mucosa. by paper and thin-layer chromatography, isotopic dilution, and the preparation of chromic acid oxidation products, acetates and methoximes, the following metabolites were identified: 5α-pregnane- 3,20-dione, 5α-pregnan-3α-ol-20-one, 5α-pregnan-3β-ol-20-one, 5α-pregnane-3β,20α-diol, Δ4-pregnen-20α-ol-3-one, and 5α-pregnan-3β-20α-diol. The major metabolic pathways of progesterone in human skin and vaginal mucosa involve reduction of the 20-one to 20α-ol, reduction of the 3-one to 3α-ol and 3β-ol, and the saturation of the 4-5 double bond to form 5α-preg-nanes. No 5β metabolites could be detected. © 1969, American Chemical Society. All rights reserved.