The in vitro effects of dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S) and related steroids on glucocorticoid corticosterone (GC) binding in hepatic cytosol and hepatic mitochondrial respiration were examined in male BHE/cdb and Sprague-Dawley (SD) rats. 2. The Kd and the IC50 for GC binding in SD rats were 5- and 2-fold higher, respectively, than in BHE/cdb rats. 3. Hepatic cytosol from BHE/cdb rats bound six times more [3H]-GC to receptors than that from SD rats. 4. The percentage displacement and Bmax of GC for its receptors were similar for the two strains of rats. 5. DHEA and DHEA-S did not displace GC from its receptors. 6. DHEA and related non-sulfated steroids decreased state 3 mitochondrial respiration, respiratory control and oxidative phosphorylation capacity in a dose-dependent manner with malate + pyruvate as substrate.