The pharmacokinetics of intravenously administered theophylline were studied in five healthy nonsmokers. Each subject received 5 mg/kg of theophylline as aminophylline after an overnight fast and again after a standard high-fat meal. Although there was wide between-day variation in the elimination rate constant in three of the five subjects, no statistically significant differences were observed in area under the time-versus-concentration curve, maximum serum theophylline concentration, elimination rate constant, or apparent volume of distribution between the two treatments. A statistical power analysis indicated that if differences in volume of distribution and maximum serum theophylline concentration occur in the general population, the mean differences are less less than 15% and 20%, respectively. This suggests that alterations in intravascular drug distribution resulting from eating a high-fat meal do not contribute importantly to previously reported effects of food on serum theophylline concentrations after oral dosing.