Using gene-targeting techniques, transgenic, knock-out (KO) mice, homozygous for the disrupted estrogen receptor alpha (alpha ERKO) and beta gene (beta ERKO) have been produced. Estrogen receptor (ER) beta expression does not appear to be dependent on ER alpha expression. Progesterone receptor (PR) mRNA is detected in alpha ERKO mice and appears to have both estrogen-independent and -dependent gene regulation. The phenotypic differences in alpha ERKO and beta ERKO mice are described. Additional studies will further define the specific roles of ER alpha and ER beta in various tissues.