Eight methylenedioxyphenyl (MDP) compounds were examined for their ability to induce cytochrome P450 (P450) in mouse liver. Induction by safrole, isosafrole, and dihydrosafrole was studied in both C57BLl6N (Ah-responsive) and DBA/2N (Ahnonresponsive) male mice after IP administration of 200 mglkglday MDP compound for 3 days. Hepatic P450 content, ethylmorphine N-demethylase, ethoxyresorufin 0-deethylase, and acetanilide hydroxylase activities were induced to the same extent in both strains of mice. Benzo(a)pyrene hydroxylase activity, however, was not induced in either C57 or DBA mice. The similarity of results in both strains of mice indicated induction of these P450 isozymes by these three MDP compounds is not mediated by the Ah receptor. Induction of P450 by butylbenzodioxole (n- butyl-BD), tertiarybutylbenzodioxole (t-butyl-BD), methylbenzodioxole (methyl-BD), nitrobenzodioxole (nitro-BD), and bromobenzodioxole (bromo-BD) was examined only in C57BL/6N mice. Methyl-BD, nitro-BD, and bromo-BD did not induce hepatic micro-soma1 proteins or selected P450 monooxygenase activities. In contrast, n-butyl-BD, and t-butyl-BD induced P450 content, ethylmorphine N-demethylase, acetanilide hydroxylase, and ethoxyresorufin O-deethylase activities. Benzo(a)pyrene hydroxylase was not induced by any of the treatments. Induction of these P450 activities is consistent with induction of P450 IIBl and P450 IA2, but not induction of P450 IA1. Western blot analysis with antibodies to P450 isozymes induced with either phenobarbital (Pb) or 3-