The 17 -hydroxysteroid dehydrogenase (17 -HSD) family of proteins regulates the levels of the active 17 -hydroxy forms of sex steroids. The expression of 17 -HSD type IV is induced by peroxisome proliferator chemicals (PPC) in rat liver. In order to characterize more generally the impact of PPC on 17 -HSD expression, we determined (1) if expression of other members of the 17 -HSD family was coordinately induced by PPC exposure, (2) the tissues in which 17 -HSD was induced by PPC, and (3) whether the induction of 17 -HSD by PPC was dependent on the peroxisome proliferator-activated receptor (PPAR ), the central mediator of PPC effects in the mouse liver. The mRNA levels of 17 -HSD I, II, and III were not altered in the liver, kidney, and testis or uterus of rats treated with PPC. The mRNA or 80 kDa full-length protein levels of 17 -HSD IV were strongly induced in liver and kidney, but not induced in adrenals, brown fat, heart, testis, and uterus of rats treated with diverse PPC. In liver and kidneys from treated rats, additional proteins of 66 kDa, 56 kDa, and 32 kDa were also induced which reacted with the anti-17 -HSD IV antibodies and were most likely proteolytic fragments of 17 -HSD IV. Treatment of mice which lack a functional form of PPAR with PPC, demonstrated that PPC-inducibility of 17 -HSD IV mRNA or the 80 kDa protein was dependent on PPAR expression in liver and kidney. Our results demonstrate that 17 -HSD IV is induced by PPC through a PPARdependent mechanism and support the hypothesis that exposure to PPC leads to alterations in sex steroid metabolism.