The effect of piperonyl butoxide or allopurinol on cyanide-induced lipid peroxidation was investigated using homogenates from whole brain of mice. The brain homogenate exposed to a low concentration of potassium cyanide (10, 50, or 100 microM) was significantly increased in their concentration of malondialdehyde (MDA) + 4-hydroxyalkenals (4-MDA) as compared to control samples, in a concentration-dependent manner. The increased lipid peroxidation induced by cyanide was inhibited by piperonyl butoxide (1 mM), an inhibitor of mixed function oxidase, but not by allopurinol (0.1 mM), an inhibitor of xanthine oxidase. Furthermore, when a brain homogenate heated at 86 degrees C for 1 min was incubated with or without cyanide at 37 degrees C for 20 min, MDA + 4-MDA levels in the homogenate were not changed between cyanide treatment and untreated. An intraperitoneal injection of piperonyl butoxide (1 g/kg) significantly inhibited cyanide-induced seizures in mice. These results suggest that cyanide-induced seizures may be partly involved in the lipid peroxidation produced by the heat unstable and piperonyl butoxide dependent factors in brain.