The role of androgen receptors in androgen-induced changes in rat adrenocortical and liver cytochrome c oxidase (COX) has been investigated. The anti-androgen, flutamide, blunted the increase in COX activity and COX subunits II/III and IV, that is seen with androgen treatment. Testicular feminized (Tfm) rats had levels of COX activity and COX subunits II/II and IV in adrenal cortex and liver that were intermediate between the high levels found in normal male rats and the lower levels of normal female rats. These data suggest that androgen effects on adrenal and liver COX are mediated through interactions with androgen receptors known to be present in these tissues. However, the observed changes in COX activity and COX subunits were not accompanied by altered levels of mRNAs encoding for COX II or COX IV.