Administration of the chemical carcinogen 2-acetylaminofluorene (2-AAF) has previously been shown to lower hepatic epidermal growth factor (EGF) binding levels during chemically induced hepatocarcinogenesis. To further characterize the specificity of this response, EGF binding levels for liver microsomes were determined after a 3-week administration of subacute doses of 2-AAF and five other known hepatocarcinogens: 3'-methyl-4-dimethylaminoazobenzene (3'Me-DAB), 2-AAF, aflatoxin B1 (AFB1), thioacetamide (TA), ethionine, benzidine (Benz), as well as four non-hepatocarcinogens: fluorene, p-aminoazobenzene, 4-acetylaminofluorene (4-AAF), and 3-methylcholanthrene. Five of six of the hepatocarcinogens tested (3'Me-DAB, 2-AAF, TA, AFB1 and Benz) caused significant lowering of EGF binding levels, and one of the four non-hepatocarcinogens (4-AAF) caused significant lowering of EGF binding levels. Paired feeding studies indicated that the decreases in EGF binding levels were not a result of differences in net diet consumption. These findings show that decreases in EGF binding capacity are caused by a diverse group of known hepatocarcinogenic compounds at an early stage in the carcinogenesis process.