Recently developed in our laboratories is an efficient extraction procedure incorporating XAD resin adsorption which yields from 200 degrees C grilled ground beef an extract containing 230 Salmonella TA1538 revertants per g fresh weight of original ground beef. These mutagenic components are specific for frameshift-sensitive Salmonella strains and have an absolute requirement for metabolic activation. S9 activation by cytochrome P-448 inducers, Aroclor 1254 (PCB), 3-methylcholanthrene (3-MC) and B-naphthoflavone (BNF), resulted in the largest mutagenic response. Phenobarbital induction gave 20% of the PCB response and Pregnenolone-16a-carbonitrile and corn oil were inactive. Human liver microsomes and BNF-induced rodent intestinal S9 were also active metabolizing fractions. Normal-phase HPLC separation of methanol-extractable metabolites generated from reaction of 2-amino-3-methylimidazo [4,5-f]quinoline (IQ), a mutagenic component of broiled food, rat liver microsomes and cofactors resulted in one direct-acting mutagenic peak and a second more polar peak still requiring metabolic activation. Two potent thermally-produced bacterial mutagens, Trp-P-2 and IQ, were examined in mammalian cells. In excision repair-deficient CHO cells, Trp-P-2 exposure caused cytotoxicity, mutagenicity (thioguanine and azaadenine resistances), sister chromatid exchange, and chromosomal aberrations at concentrations more than 30-fold lower than those for IQ. In normal repair-proficient CHO cells Trp-P-2 was one-half as active and IQ was inactive. Relative to Trp-P-2, IQ is much more potent in the Salmonella bacterial system than in mammalian CHO cells.