Responsiveness of the liver to estradiol-17β was examined immunologically by measuring the amount of female-specific serum proteins (FSSP) in the serum of the sand lamprey, Lampetra reissneri, injected with estrogen. FSSP synthesis was clearly induced in adult males and young adult lampreys of both sexes by two injections of estradiol-17β, at 200μg/animal 3 days apart, while the same treatment was quite ineffective in ammocoetes larvae. Induction of FSSP synthesis was successful in some ammocoetes when estradiol-17β injections (200μg/animal) were done once a week for three weeks. Discussions were made on the development of responsiveness of the liver to estrogen during ontogenesis of the sand lamprey.