Genomic and complementary DNA fragments encoding an estrogen receptor (ER) homolog were cloned from the medaka fish, Oryzias latipes. The genomic DNA contains nine introns. The cDNA encodes a protein of 620 amino acids that is composed of the complete set of the conserved ER domains. Sequence comparison among fish and human ER genes suggests that the human gene may have lost two introns during the evolution. ER-specific mRNA was expressed in large amounts in adult tissues such as brain, ovary, testis, and female liver. As expected by the fact that embryos and fry are highly sensitive to and sex-reversed by estrogen, ER mRNA was detected in them but at a basal level. Oral administration of estrogen elevated the hepatic expression of ER mRNA, suggesting an autoregulatory loop for transcriptional activation. However, estrogen did not affect the expression in embryos and fry, suggesting that the positive loop is silent at the juvenile stage and that the basal expression is not due to the absence of estrogen. We also found that estrogen inhibits the embryonic development of blood vessels, providing a new, simple method of bioassay for estrogenic activity.