RETINOIDS, naturally occurring and synthetic analogues of vitamin A, are involved in the maintenance and differentiation of epithelial tissue 1-3. Furthermore, it has been reported that these compounds inhibit the growth of certain nontransformed and virally and chemically transformed cell lines4,5. Recently, it has been shown that retinoic acid stimulates the differentiation of embryonal carcinoma cells6,7, undifferentiated early embryo-like cells present in teratocarcinomas. Embryonal carcinoma cell lines differ widely in their capacity to differentiate: a distinction has been made between 'pluripotent' and 'nullipotent' cell lines8,9. In contrast to the latter, Pluripotent embryonal carcinoma cells differentiate when injected into mice8 or when cell aggregates are formed in vitro 10; some cell lines differentiate quite readily even when grown in monolayer culture. We have shown7 that retinoic acid not only stimulates the differentiation of Pluripotent embryonal carcinoma cell lines, but also induces differentiation of the so-called nullipotent embryonal carcinoma cell lines nulli SCC1 and 6050 AJ. We show here that this effect is not limited to retinoic acid but that several other retinoids have the ability to stimulate differentiation of at least one embryonal carcinoma cell line, PCC4.aza1R. Furthermore, we present evidence to suggest that the action of retinoids may be mediated by a retinoic acid binding protein. © 1979 Nature Publishing Group.