It has been postulated that reversible, high-affinity binding of 3-methylcholanthrene(MC)-type inducers to a receptor protein (the Ah receptor) in hepatic cytosol is essential for induction of aryl hydrocarbon hydroxylase (AHH) enzymic activity. To test this postulate, the binding affinities of 16 highly-purified, synthetic chlorinated biphenyl (PCB) congeners, which have been categorized either as phenobarbitone(PB)-, MC- or mixed (PB + MC)-type inducers of cytochrome P-450-dependent monooxygenase have been examined. The affinity of individual biphenyl congeners for the receptor was determined by their competition with 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin ([3H]TCDD) for specific cytosolic binding sites as measured by sucrose density gradient analysis following dextran-charcoal treatment. This assay demonstrates (a) that the receptor binds with highest affinity to 3,3', 4,4',5-pentachlorobiphenyl and 3,3',4,4'-tetrachlorobiphenyl ('pure MC-like' inducers); (b) mixed-type PCB inducers also bind to the receptor but with an affinity (average EC50-value of 8.6 microM) lower than that for 3,3',4,4',5-pentachlorobiphenyl; this corresponds with their relatively lower potencies as AHH inducers; (c) the receptor binds 2,2',4,4'-tetra-, 2,3,4,5-tetra-, 2,2',4,4',5,5'-hexa- and 2,3',4,4',5',6-hexachlorobiphenyl at high concentrations (0.1 mM), whereas PB fails to bind, even at a concentration of 10 mM. All PCBs tested competed with [3H]TCDD for Ah receptor, but there was a great variation in their relative binding affinities. The fact that two chlorinated biphenyls classed as 'PB-like' inducers and two chlorinated biphenyls which are neither 'PB- nor MC-type' inducers competed, coupled with the fact that PB did not bind to the receptor suggest that chemicals other than "pure MC-type' inducers can bind to the cytosolic receptor. Affinity of the binding dictates the relative potency of given PCB congeners as inducers of cytochrome P-448.