Unless they are taken at unacceptably frequent intervals, conventional rapid-release theophylline tablets and liquids produce excessive serum concentration fluctuations, particularly in patients with rapid elimination. Slow-release formulations provide more stable serum concentrations with longer dosing intervals if absorbed completely, consistently, and at a sufficiently slow rate and thus have the potential to improve efficacy and compliance. However, there are clinically important differences in the extent and rate of absorption among the 15 slow-release formulations available under 29 brand names in the United States. Fluctuations in steady-state serum concentrations are a function of the absorption rate of the product, the elimination rate of the patient, and the dosing interval. In patients with slow elimination, clinically relevant differences among formulations are not apparent with twice-daily dosing. Among patients with more rapid elimination, however, available data for only two products demonstrate sufficiently slow absorption to justify routine twice-daily use without excessive fluctuations. More rapidly absorbed formulations must be administered at 8-hour intervals in such patients to prevent breakthrough in asthmatic symptoms before the next dose, despite promotional claims to the contrary. Current products approved for "once-a-day" dosing are clinically inadequate because of incomplete or erratic absorption or excessive serum concentration fluctuations. Lastly, food intake induces dose dumping of potentially toxic amounts of theophylline from Theo-24 and greatly impairs absorption from Theo-Dur Sprinkle capsules but has no important effect on Theo-Dur tablets. The effects of food on most other theophylline products are not known.