The sialic acid content and the activities of the enzymes responsible for the activation, transfer, and hydrolysis of sialic acid were determined in the livers of male Sprague-Dawley rats maintained on diets containing the hepatocarcinogen 2-acetylaminofluorene (AAF). The incidence of hyperplastic lesions was modulated by dietary fat and by the presence of a synthetic antioxidant. The purified diets utilized differed in the amount and degree of unsaturation of the lipid component; they contained either 20% corn oil, 18% coconut oil + 2% linoleic acid, or only 2% linoleic acid, and each diet was prepared either with or without 0.3% butylated hydroxytoluene (BHT). The supplementation of diets with BHT greatly retarded the development of hyperplastic nodules compared to unsupplemented diets. The AAF-treated rats and age-matched controls fed AAF-free diets were killed after a 12 to 17-week period of dietary treatment, and the livers were removed for histological and biochemical studies. Significant increases in sialic acid content, and in the activities of CMP-sialic acid synthetase and neuraminidase were observed in the livers from AAF-treated rats. The BHT supplementation of the AAF-containing diets resulted in livers with lower levels of sialic acid and CMP-sialic acid synthetase activities. The chemical and enzymatic changes observed in AAF-treated rats are consistent with an increased turnover of sialoglycoconjugates during the carcinogenic process.