Administration of butylated hydroxyanisole (BHA), a widely used food additive, has been found to inhibit the carcinogenic and toxic effects of various chemicals in animal models. To study the relationship of dietary BHA to the acute toxicity of methylazoxymethanol (MAM) acetate, a colon-specific carcinogenic compound, groups of female CF1 mice were fed NIN-07 diet containing 0, 300, 1000, 3000 or 6000 ppm BHA or a semipurified diet containing 0 or 6000 ppm BHA for 4 wk, and were injected ip with MAM acetate (20 mg/kg body weight) at the end of the first 2 wk and again 4 days later. At levels of 300-6000 ppm, BHA was found to protect against death caused by MAM acetate. The mortality rates in MAM-treated mice were 80 and 92% in those fed the diets with no BHA and 0 and 1% in those fed 6000 ppm BHA, and were inversely related to the amount of BHA in the diet. The protection was associated with increased levels of hepatic cytochrome P-450 and b5 and with a reduction in necrotic changes in the liver.