Expression of the new 17-hydroxysteroid dehydrogenase, type 10 (17-HSD-10), formerly known as endoplasmic reticulum-associated amyloid-binding protein (ERAB), has been investigated in the testes of various mammals under normal and perturbed conditions. Results show that 17-HSD-10 is a major product of both fetal and adult-type Leydig cells. In the former, protein persists until late in postnatal development, and in the short-day hamster model does not disappear when Leydig cells involute. During puberty in the rat, immunohistochemical staining for 17-HSD-10 in adult-type Leydig cells first becomes evident on day 20, increasing to maximal staining intensity by day 35. In the rat, but not in the mouse or any other species examined, there is also staining in late spermatids. Examination of testes from rats subjected to perinatal treatment with either a GnRH antagonist or low and high doses of diethylstilbestrol, revealed that expression of 17-HSD-10 follows closely Leydig cell differentiation status, correlating with 3-HSD expression in a previous study. In aging (23 months) rat testes, Leydig cell, but not germ cell immunostaining for 17-HSD-10 is markedly reduced. 17-HSD-10 appears to preferentially convert 3-androstanediol into dihydrotestosterone, and estradiol to estrone. Thus perinatal expression of this enzyme in fetal Leydig cells may contribute to protecting these cells from estrogens and encourage androgen formation.