Theophylline concentrations in plasma and urine were determined during maintenance treatment in nine healthy volunteers during one dosage interval before and after 10 days of simultaneous treatment with pentobarbital (100 mg each night). During the pentobarbital period, total plasma clearance of theophylline increased by 40% (range -4-79%), whereas renal clearance remained unchanged. It is concluded that therapeutic doses of pentobarbital induce the metabolism of theophylline with marked interindividual variation.