A specific high-affinity oestradiol-binding protein was characterized in salt extracts of liver nuclei of the developing chick embryo. It is present in very small amounts at day 10 of development and is marginally stimulated by oestradiol injection into the yolk sac on day 8. Injection of oestradiol on day 10 evokes a substantial increase in the nuclear oestradiol-binding activity measured on day 12 of development. This oestradiol-binding protein has properties of sedimentation, hormone specificity and high-affinity binding very similar to those of the soluble nuclear receptor in hatched chicks. Livers from the 12-day embryos injected 48 h earlier with oestradiol do not synthesize vitellogenin, as judged by a specific immunochemical and electrophoretic assay for this oestrogen-induced protein. Traces of vitellogenin synthesis can be induced in 13-day-embryo liver, and a substantial response, equivalent to that in hatched chicks, is seen in liver from 15-day embryos injected on day 13. The development of the ability of oestradiol to increase the concentration of the soluble nuclear receptor appears to be one, but not the only, critical factor involved in the development of the ability of chick liver to synthesize vitellogenin.