To evaluate the bioavailability of a new theophylline preparation suitable for once-a-day (od) oral administration, we performed a nonrandomized crossover study in which the absorption of the OD and a standard twice-a-day (bid) preparation were compared. Eight stable asthmatic patients, after having achieved steady-state, received an average of 975 mg of OD preparation at 8 PM. The protocol was later repeated with the same subjects receiving 487.5 mg of the bid preparation at 8 PM and again at 8 AM using the same total dose. The maximal mean serum concentrations were 15.5 +/- 1.6 (SEM) micrograms/ml for the od preparation on the 8th hour and 12.7 +/- 2.2 for the bid regimen. The trough level was 7.4 +/- 1.2 micrograms/ml for the od regimen and 10.6 +/- 1.6 for the bid regimen. With either regimen, therapeutic theophylline levels could be observed throughout the 24-hour study period. Anhydrous theophylline may be administered as a single daily dose agent.