Theophylline clearance was examined in 23 children with chronic asthma by administering constant intravenous infusions of theophylline until steady-state serum concentrations were documented. Clearance was subsequently related to peak and trough serum concentrations during a multiple-dose oral theophylline regimen. Although theophylline clearances tended to decrease with age, considerable interpatient variability was observed. Clearances correlated inversely with a standardized index of serum concentration response to oral dosage resulting in a wide range of dosage requirements to maintain therapeutic serum concentrations of 10 to 20 microgram/ml. Intrapatient variability over an interval up to seven months, however, was acceptably small, suggesting that dosage requirements, once established for an individual, should remain relatively stable under normal conditions. Differences in serum theophylline values during a 6-hour dosing interval among children who were receiving theophylline on a continuous basis correlated with clearance and averaged 9 +/- 3 microgram/ml (mean +/- SD), exceeding to 10 microgram/ml interval width of the therapeutic range among 40% of the children. This observation supports the clinical need for reliable sustained-release preparations of theophylline for children who are receiving continuous therapy in order to avoid unrealistically short dosing intervals.