Male F-344 rats, when treated with either 150 mg/kg or 300 mg/kg body weight of DHEAS for 14 days, produced a dose-dependent increase in liver weight and peroxisomal β-oxidation activity, characteristic of peroxisomal proliferation. Contrary to previous observations in vitro, we also found a significant increase in catalase activity in rat liver with the higher dose of the steroid. Furthermore, the in vivo induction of peroxisomal β-oxidation by DHEAS observed in our study was significantly less than reported in vitro, and also unlike previously reported in vitro results, was approximately equivalent to DHEA administered in vivo.