Gene knockouts in mice have been reported for the glucocorticoid, estrogen, and progesterone receptors, and a natural gene knockout, the testicular-feminized mouse, exists for the androgen receptor. Of these knockouts only the glucocorticoid receptor knockout has profound effects on embryonic development, with defects in the lung and adrenal gland causing perinatal lethality. Female mice with either the estrogen or progesterone receptor knocked out are infertile, as are male mice lacking the estrogen receptor, which have smaller testes and lower sperm production. Estrogen receptor knockout mice also suffer osteoporosis. Progesterone receptor knockout mice fail to display ovarian follicular rupture and normal sexual behavior. Steroid receptor knockout mice thus provide a useful animal model for further studies on steroid action. Recent results with Cre- and FLP-recombinase promise a new generation of gene-targeted mice by production of tissue-specific and ligand-inducible gene knockouts.