The elimination rate for theophylline varies greatly among patients, but recommendations for maintenance dosing schedules have assumed relatively little intrapatient variability even over extended time periods. Reports of large intrapatient variability of theophylline elimination rate and consequent clearance raise concerns regarding this assumption and also challenge the practice of assuming relative constancy of elimination rate in the performance of bioavailability studies of slow-release formulations. We therefore systematically studied under controlled conditions the elimination rate of theophylline in 10 patients over an extended time interval. The initial elimination rate constants ranged from 0.062 to 0.136 hours-1. The changes ranged from -5.9% to 9.4% of the initial value during intervals of 2 to 11 months. Correlation of the first and second values was 0.96. Thus the elimination rate of theophylline generally appears to vary little within individuals over time when studied under controlled conditions.