The activities of mitochondrial, manganese-containing superoxide dismutase (MnSOD) and cytoplasmic, copper-zinc-containing superoxide dismutase (CuZnSOD) were measured in subcellular fractions of whole brain homogenates prepared from intact and gonadectomized (GDX) male rats, untreated or treated subcutaneously (sc) with a single dose of 2 mg progesterone (P) and/or 5 micrograms estradiol benzoate (EB). Neither MnSOD nor CuZnSOD was affected by the removal of the testes. Similarly, CuZnSOD activity was steady following systemic administration of P and/or EB to intact and GDX animals 2 h or 24 h prior to sacrifice. On the other hand, both P and EB suppressed MnSOD in the brain of either intact or GDX rats. These results suggest involvement of P and EB in the control of MnSOD activity in the brain of male rats.