Nonspecific esterase of mouse epididymis has previously been studied histochemically, using alpha naphthyl-acetate and 5-bromoindoxyl acetate techniques, as well as certain inhibitors. Epithelial cell types of the epididymis have been characterized, and certain esterase isozymes in a particular cell type, is shown to be androgen dependent. When mice of different strains were castrated or treated with antiandrogens, the characteristic histochemical reaction product disappeared or was greatly reduced. Androgen treatment of castrated animals caused the reaction in the cells concerned to return to normal. This method can now be applied to the study of epididymides of genetically sex-reversed chromosomal female, to analyze genetic control of X-chromosomal activation.