Three groups of isomeric nitrogen heterocycles, phenylpyridines, phenylimidazoles and pyridylimidazoles were studied in relation to the effect of steric factors on type II binding to cytochrome P-450 and inhibition of aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) activity in hepatic microsomes from phenobarbital(PB)- and beta-naphthoflavone(beta NF)-induced rats. Type II binding affinity was lower (higher Ks) in compounds with substituents on the carbon adjacent to the nitrogen undergoing ligand interaction than in those where steric hindrance near the nitrogen was minimal. Binding affinities of the compounds as measured by their Ks values, were quite similar in both PB- and beta NF-induced microsomes. In PB-induced microsomes, type II binding affinity was generally reflected by the ability of the compounds to inhibit AHH activity. In contrast, most of the compounds evaluated were inactive as AHH inhibitors in beta NF-induced microsomes.