Sustained-release theophylline formulations are designed to provide consistent serum theophylline concentrations (STCs) by influencing the rate of theophylline absorption. The objective in developing these formulations is to minimize fluctuations in STC and improve patient compliance. Recent information, however, suggests that certain patients are susceptible to significant day-to-day and dose-to-dose variations in STC. The purpose of this discussion is to review information on conditions that affect theophylline absorption. These factors include the formulation, dosing interval, age of the patient, absence or presence of food, and gastrointestinal physiology. Appreciation of the potential variation in STC, secondary to inconsistencies in theophylline absorption, is important in the accurate interpretation of STC obtained during routine therapeutic monitoring.