Advances have recently been made in understanding the pharmacokinetics of theophylline. To correlate the new knowledge of theophylline pharmacokinetics with the drug's current status in therapy, we have critically reviewed the relevant investigations of the last 5 years. We consider data on its presumed mechanisms of action, factors affecting its clearance, its use in pregnancy, treatment of overdoses, and important drug interactions. Theophylline clearance is decreased by concomitant use of erythromycin, cimetidine, high-dose allopurinol, oral contraceptives, and caffeine. Clearance is increased by concomitant use of phenobarbital and phenytoin. Newly discovered actions of theophylline include dose-dependent improvement of diaphragmatic contractility, augmentation of ventilatory response to hypoxia, and sleep disturbances (especially with high-dose treatments). Points clinically relevant to the daily use of theophylline derivatives and the importance of sustained-release preparations are discussed. Theophylline continues to play a major role in therapy for reactive airways disease.