The effect of oral administration of sucralfate concurrently with a single oral dose of non-sustained-release theophylline was studied in eight healthy male volunteers. A two-way, randomized, cross-over study design was used. During the control phase, each subject received a single 5-mg/kg dose of a non-sustained-release theophylline product. During the treatment phase, a 1-g sucralfate tablet was ingested four times a day for two days before the theophylline dose, with the theophylline dose, and six hours after the dose. Plasma samples were collected at frequent intervals for 24 hours after theophylline dosing. Plasma theophylline concentrations, determined by high-performance liquid chromatography, were similar in the absence and presence of sucralfate. No significant differences in theophylline half-life or mean residence time between the control and treatment phases were observed. A significant decrease in the area under the plasma drug concentration-time curve was observed in the presence of sucralfate. However, the magnitude of this change was minimal and unlikely to be clinically important. In these healthy subjects, the concomitant administration of sucralfate with a single dose of non-sustained-release theophylline did not alter the rate or extent of theophylline absorption to a clinically important degree.