Heterologous antisera against rat yolk sac made in rabbits and sheep produced congenital malformation, fetal growth retardation, and embryonic death when injected into pregnant rats. Antigens present in the cellular or acellular portions of the yolk sac were capable of producing teratogenic antibodies. Fluorescence-labeling techniques revealed that yolk-sac antiserum contained antibodies that reacted strongly with the nonserum-protein antigens of maternal adrenal, ovary, and kidney; fetal yolk sac; and chorioallantoic placenta. Teratogenic yolk-sac antiserum localized in the noncellular and intracellular portions of the parietal and visceral yolk sac including Reichert's membrane. It is postulated that yolk-sac dysfunction is produced by the localization of these antibodies in the yolk sac. The localization of yolk-sac antiserum in the yolk sac was observed at term regardless of whether the antiserum was injected on the 11th or 20th day of gestation, although the time of injection affected the localization at term qualitatively and quantitatively. These results suggest that further studies of the functions of the yolk sac at various periods of gestation are indicated not only in rodents but in humans since the yolk sac may play a role in human teratogenesis. The unanswered questions concerning yolk-sac function and dysfunction in rodents and the importance of the yolk sac in humans add another aspect to the problem of transferring the results of teratogenic studies in rodents to the human situation.