Two sustained-release formulations of theophylline, tablets (T) and microgranules (MG) forms, were administered in a randomized order to 8 healthy subjects in fasting or with a high-protein test meal (50 per cent). Blood was collected for 32h post-dose. In fasting subjects, absorption of theophylline was significantly faster for T (tmax 5 h) as compared with MG (tmax 8 h, p less than 0.05), but Cmax and AUC were comparable; intersubject variability was higher with T. Administration of a high-protein test meal with T produced a significant decrease of the zero-order absorption rate constant of theophylline (K omicron 37.8 +/- 9.1 mgh-1 after meal versus 58.8 +/- 13 mgh-1 in fasting, p = 0.01), tmax was doubled to 10 h, and Cmax increased by 25 per cent (6.33 +/- 2.16 mgl-1 versus 5.04 +/- 1.28 mgl-1, p less than 0.02); with MG, tmax were the same (8 h), Cmax were not significantly increased (4.79 +/- 0.84 mgl-1 versus 4.55 +/- 0.67 mgl-1), absorption was delayed (lag-time 1.28 +/- 0.58 h) and the absorption was slightly accelerated (K omicron 50.4 +/- 10.4 mgh-1 versus 42.3 +/- 11.9 mgh-1, NS). For each form bioavailability was not significantly modified by food. This study demonstrated that food rich in protein modifies the absorption rate of theophylline in a sustained-release tablet formulation but is without influence in a pH-independent, sustained-release microgranule formulation.