The metabolism of C14-17[beta]-estradiol was studied in the human placenta perfused in vitro. Four placentas were perfused for eight hours each with a change of perfusing fluid every hour. Perfusates for 15 of the 32 hours were analyzed individually for metabolites of the radioactive estradiol added at the beginning of the various hours. In addition, 1 placenta was subjected to extraction at the end of the perfusion. The radioactive metabolites were identified by paper chromatography, countercurrent distribution, and derivative formation. The possible effect of human chorionic gonadotropin (HCG) on the formation of metabolites was studied as follows HCG was not added during perfusion I; HCG was added during each hour of perfusion II; in perfusions III and IV HCG was added only during the last five and four hours respectively and not during the first three and four hours. C14-estriol was not found in the perfusates for hours 2, 4 and 7 respectively of perfusion I (no HCG). C14-estriol was found in the perfusates for hours 2, 4 and 7 respectively of perfusion II (with HCG). In perfusion III no C14-estriol was found in the perfusate for hour 2 (no HCG), but it was identified in the perufsates for hours 4, 6 and 8 respectively (with HCG). No C14-estriol was found for hour 4 (no HCG) or hours 7 and 8 respectively (with HCG) of perfusion IV. C14-estriol was also found in the extract of the placenta from perfusion III. The proportion of radioactivity recovered as C14-estriol ranged from 0.7 to 4.5 per cent. These experiments demonstrate that the human placenta is capable of converting estradiol to estriol. The conversion has thus far been observed only when HCG was added to the perfusing fluid. This apparent effect of HCG on estrogen metabolism points to a possible role of HCG in placental self-regulation. C14-2-methoxyestrone was tentatively identified in the perfusates for hour 4 of perfusion II, in the perfusates for hours 4, 6 and 8 respectively of perfusion III, and in the extract of the placenta from perfusion III (0.7 to 2.0 per cent). C14-16-epiestriol was tentatively identified in the perfusate for hour 4 of perfusion II and in the extract of the placenta from perfusion III (about 1 per cent of recovered radioactivity). C14-estrone was identified in each perfusate (58-82 per cent).