In a single-dose crossover study with 16 healthy male nonsmoking volunteers the absorption profile and absolute bioavailability of the sustained release pellets contained in all dosage strengths of Bronchoretard (100, 200, 350, 500 mg anhydrous theophylline) were investigated. One capsule (500 mg theophylline) was given after an evening meal. The reference treatment consisted of an i.v. infusion over 8 h in a total dosage of 350 mg theophylline. Plasma concentration-time profiles were evaluated for 72 h after dosing, respectively start of infusion. Theophylline was measured by high-performance liquid chromatography (HPLC). Absorption profiles (Wagner-Nelson) were derived and the absolute bioavailability was calculated. For the sustained release pellets a liberation/absorption of zero order for 12 h could be noted; the dose-corrected mean absolute bioavailability was 88%. The assumptions of an investigation on absolute bioavailability are discussed and the limitations on generalizability resulting therefrom.