Liver volume and antipyrine disposition have been investigated in healthy premenopausal women who received 30 µg ethinyl oestradiol + 500 µg dl-norgesterol as an oral contraceptive. Six months- treatment was associated with a 17% increase in liver volume while no change occurred in age-matched control subjects. In the same subjects the contraceptive decreased antipyrine clearance by 21%. Thus the contraceptive markedly reduced drug-metabolizing activity per unit volume of liver by 33%. In additional subjects, discontinuation of the contraceptive resulted in a 30% increase in antipyrine clearance. These observations confirm that conventional oral contraceptive therapy to premenopausal women increases hepatic size and that it is a potent inhibitor of drug-metabolizing activity.