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A study was conducted to determine if a monoclonal antibody (MAB), H222, prepared against human breast cancer estrogen receptors (ER) would recognize ER in the oviduct and liver of garter snakes (Thamnophis sirtalis parietalis). Using sucrose gradient analysis of antibody-ER complexes bound to [3H]estradiol we have determined that the MAB H222 binds to an ER in the cytosolic and nuclear extracts of snake tissues. The snake ER is not bound by nonspecific MABs in the sucrose gradient analysis. Further, the snake ER does not bind to other steroids, including a synthetic progestin, R5020, or the androgens 5 alpha dihydrotestosterone and R1881. The quantity of ER in the snake oviduct (200-700 fmol/mg DNA) is within an order of magnitude of that found in the oviduct of the nonhuman primate. These results suggest that the MAB H222 and 17 beta-estradiol bind to an ER in the snake that shares common properties with mammalian ER.