In two studies, 25 diurnally active patients with asthma (6 to 17 years of age) were evaluated at steady state for day-night differences in serum theophylline concentration (STC) by frequent blood sampling over two consecutive 12-hour dosing intervals while being given treatment with Theo-Dur. In both studies findings were similar; Cmax was greater and Tmax shorter after dosing at 7 A.M. or 8 A.M. versus 7 P.M. or 8 P.M., with Cmax-C min approximately 7 micrograms/ml. For the morning dosing, 22 of 25 patients exhibited Cmax within 4 hours; 23 of 25 exhibited C min 12 hours after dosing. For the evening ingestion, the situation was very different: C min occurred within the initial 4 hours in 22 of 25 patients, whereas Cmax occurred in 22 of 25 patients just before the next (morning) dose. The findings indicate that the most appropriate time to estimate Cmax in patients given Theo-Dur is within the 4 hours after morning ingestion. The best time to estimate C min is a few hours after the evening ingestion. Sampling at these times is likely to represent within 10% to 20% the actual Cmax or C min.