In order to determine whether human umbilical cord blood erythrocytes are capable of progesterone biosynthesis, sonicated preparations of plasma-free erythrocytes at the range of total cell numbers between 18.4 × 10<sup>9</sup> and 62.9 × 10<sup>9</sup> cells obtained from umbilical cord arterial and venous blood collected from normal pregnant women (n = 6, age 28–39 years) following spontaneous vaginal delivery were incubated with [7n-<sup>3</sup>H]-pregnenolone as substrate. The leucocyte content of the incubates was negligible (<0.005%). Controls (n = 4, age 29–36 years; 27.6 × 10<sup>9</sup> to 42.7 × 10<sup>9</sup> erythrocytes) obtained from cord blood of normal pregnant women were heat-denatured preparations of cells. Using the reverse-isotope dilution technique, [<sup>3</sup>H]-progesterone was isolated and characterized yielding an overall enzymic conversion which ranged between 0.27 and 0.46%. The results indicate for the first time that cord blood erythrocytes possess the 3β-hydroxysteroid dehydrogenase-5,4-en isomerase activity and are a source of progesterone in human pregnancy.