The oestrogen receptor (ER) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding and activation of transcription. We show here that the human ER gene is greater than 140 kb in length, split into eight exons and that the positions of these introns have been highly conserved when compared with the chicken progesterone receptor and are remarkably similar to those of one of the chicken thyroid hormone receptor genes. The N-terminal A/B region, which is not conserved between the different members of the nuclear receptor family, is almost entirely encoded within a single exon. Notably each of the putative 'zinc fingers' of the receptor DNA-binding domain is encoded separately, and the hormone-binding domain is assembled from five exons. In addition, we find that the ER isolated from the human breast cancer cell line MCF-7 contains a Gly-400----Val mutation present in the hormone-binding domain.