Mutant mice deficient in glucose-6-phosphate dehydrogenase were used to induce teratomas. This enzyme is linked to the X chromosome, which can be inactivated in female embryo. The differences in the enzyme activity between yolk sac mesoderm and embryo versus yolk sac endoderm can be detected in female concepti by using appropriate crosses of wild-type and G6PD-deficient mice. Histochemical study showed that the dual cell population was observed in heterozygous embryos and in the embryomas derived from them. The teratomas derived from the corresponding yolk sac, however, were G6PD-positive from wild-type and G6PD-negative from homozygous enzyme-deficient mothers. We conclude that yolk-sac-derived teratomas are of endodermal origin because of the fact that the paternal X chromosome is inactivated in the yolk sac endoderm, whereas in the yolk sac mesoderm, as in the embryo, the inactivation is at random.