Tumor markers CA 125 and CA 19-9 are elevated in a variety of malignancies in adult patients, but only little is known of their biology during gestation or infancy. We have addressed the developmental pattern of these carbohydrate antigens in pediatric patients by measuring their serum levels in 133 cord blood samples from the second through third trimester of gestation and in 39 infants aged less than 1.5 y. The serum concentrations of both markers revealed developmental changes, the levels being higher at earlier gestation (wk 24 through 37) than at term or during infancy. The clinical value of the markers was evaluated by monitoring 26 children with germ cell tumors; 14 benign and 2 immature teratomas, and 11 malignant germ cell tumors. Patients with immature sacrococcygeal teratomas showed constant and prolonged elevations of serum CA 125 and CA 19-9. In contrast, all but two children with mature teratomas had normal marker levels; these two patients with abnormally high serum CA 125 and CA 19-9 values for the first 4 postoperative weeks had a benign ovarian and ventricular teratoma, respectively. Of the 11 children with malignant germ cell tumors, serum CA 125 or CA 19-9 concentration was elevated in four patients at diagnosis and declined to normal within 2 wk after institution of therapy. Malignant recurrence in two patients was not associated with a reelevation of the CA 125 level. Taken together, our results demonstrate a developmentally regulated pattern of serum CA 125 and CA 19-9. The carbohydrate markers were usually inferior to alpha-fetoprotein in monitoring of germ cell tumors, but may be a useful adjunct in the follow-up of immature teratomas.