The eects of age on hepatic microsomal enzyme induction were studied in male CD-1 mice. Six week old and 1 year old animals were treated with either phenobarbital (80 mg kg 71 ) or saline once daily for 3 d. Twenty-four hours after the last treatment, animals were sacri®ced and livers were harvested. Hepatic microsomal fractions were isolated and incubated with alprazolam, a triazolobenzodiazepine metabolized by cytochrome P-450-3A isoforms in humans. Metabolites were identi®ed and quantitated by HPLC. All microsomal preparations produced two principal metabolites (a-OH-and 4-OH-alprazolam) while microsomes from phenobarbital-treated animals also produced a third metabolite (a, 4-dihydroxyalprazolam). V max , K m , and intrinsic clearance (V max / K m ratio) for both a-OH-and 4-OH-alprazolam in the saline-treated control animals were not signi®cantly dierent between age groups. V max and intrinsic clearance for both metabolites were more than three times greater in phenobarbital-treated animals than in the control mice (p<0´001). Age did not in¯uence the extent of induction, and both pathways were induced to approximately an equal extent. Thus the present in vitro study of liver microsomal preparations from male CD-1 mice does not delineate a mechanism for impaired alprazolam clearance in aging organisms in vivo. There is no evidence that age alters susceptibility to induction by phenobarbital. &1997 by John Wiley & Sons, Ltd.