The estrogen receptor (ER) exists in two known forms, ERalpha and ERbeta, and acts as a ligand-inducible transcription factor to fulfill critical roles in reproductive physiology. Although in vitro studies suggest the ERs may play redundant roles, a dissimilar tissue distribution indicates otherwise. Therefore, to gain insight into the role of each ER form, individual lines of mice lacking each respective receptor, as well as mice lacking both ER forms, were generated. alphaERKO and betaERKO female mice possess a normally developed reproductive tract and maintain expression of the opposite ER. The alphaERKO female is infertile and exhibits a hypoplastic uterus that is refractory to estrogens. The ovaries of the alphaERKO female are consistently polycystic and lack indications of spontaneous ovulation. In contrast, the betaERKO female exhibits a hormonally responsive uterus and grossly normal ovaries, but is subfertile in terms of the frequency and size of litters. Immature females of both ERKO lines successfully ovulate viable ova when superovulated with exogenous gonadotropins, yet the average yield of ooctyes is reduced. Mice lacking both known ER forms (alphabetaERKO) are infertile, possess the expected reproductive tract structures, but exhibit a remarkably distinct ovarian phenotype characterized by postnatal loss of oocytes and redifferentiation of the remaining somatic cells to Sertoli-like cells. This "sex-reversal" in the alphabetaERKO ovary is accompanied by the ectopic expression of testis-specific genes, for example, Sox9 and sulfatedglycoprotein-2.