The production of alpha-fetoprotein (AFP) by human germ cell tumors was studied in surgical specimens, cultured cells and transplanted tumors in nude mice. AFP was detected most frequently in yolk sac (endodermal sinus) tumors, and it was also detected, though only occasionally, in embryonal carcinomas and in teratomas. AFP-positive cells in teratomas presented a glandular or hepatoid appearance. Our experimental data suggest that AFP production in embryonal carcinomas is due to the functional expression of yolk sac differentiation preceding its morphologic expression. Although the transplanted tumors maintained the productivity of AFP, the cultured cells were not successful in maintaining a continuous AFP production.