Dosing intervals for sustained-release theophylline preparations depend on the rate of formulation absorption, the rate of elimination by the patient, and clinically acceptable fluctuations in serum concentration. A comparative study of intersubject variation in fraction absorbed-time profiles, a process-independent method of comparing rates of absorption, was performed with 6 sustained-release preparations in 6 healthy male volunteers. The sulphasalazine/sulphapyridine method of assessing orocaecal transit time was implemented so that upper gastrointestinal and colonic absorption could be estimated. Time until 90% absorption varied from 4.43 hours to 7.46 hours and the mean percentages of theophylline remaining to be absorbed from the colon were limited to between 7.5% and 29.7% with the various formulations. There was a great intersubject variability in the rate of theophylline absorption and also considerable differences among the volunteers in their formulation-to-formulation absorption profiles. Promotional literature depicting mean or group data masks this variability in absorption profiles. Because host factors related to gastro-intestinal physiology impose highly variable theophylline absorption profiles on sustained-release formulations, it is technically impossible to formulate a suitable once-a-day product for the majority of patients.