The metabolism of iv-administered 14C-cortisol (F) by pregnant baboons (107, 124 and 150 days gestation) was compared with that previously reported for nonpregnant animals and with that of animals examined 6-18 h after spontaneous vaginal delivery (178 plus or minus 4 days). Unconjugated, glucuronoside (beta-glucuronidase) and sulfate (H2SO4-ethyl acetate) fractions were extracted with ethyl acetate from urine containing more than 80% of injected 14C. Metabolites of interest were isolated by paper partition chromatography and purified by crystallization and derivative formation. Compared with nonpregnant animals, the following changes (P less than 0.05) were observed in pregnancy: (1) an increase in the percent urinary 14C in the unconjugated fraction and a decrease in the proportion of 14C appearing in the glucuronoside fraction; (2) an increase in excretion of metabolites more polar than the cortols; (3) a decrease in excretion of metabolites less polar than cortisone in the glucuronoside fraction; (4) an increase in unconjugated F excretion. Production rate of F (11.9 plus or minus 0.7 mg/day) estimated by isotope dilution and percent urinary 14C in tetrahydrocortisol and tetrahydrocortisone from the glucuronoside fraction were as in nonpregnant animals. With the exception of an increase in F production (22.7 plus or minus 0.8 mg/day), presumably the result of the stress of labor, F metabolism in the immediate postpartum period was strikingly similar to timals indicates that changes in the mother alone can account for the altered metabolic disposition of F in pregnancy and suggests that the fetus takes little part in metabolism of maternal circulating F.