Fischer 344 rats were fed a low-fat high carbohydrate diet (HC), an isocaloric fat-containing diet (IC), a hypercaloric fat-containing diet (HF) or rat chow. Covalent binding of AFB, to liver DNA, RNA and total proteins was investigated in a 24 hour period following administration of a single intraperitoneal dose of AFB, (I mg/kg body weight). AFB1 binding to nucleic acids was greatest in the HC and was generally significantly lower (p < 0.05) in the HF, IC and rats fed chow. The results suggest that fat decreases hepatic macromolecular adduct formation by inhibiting activation of AFB1 to the epoxide or by enhancing the activity of detoxification pathways.