Nocturnal worsening is an important problem in asthma management. We evaluated the efficacy of two sustained-released theophylline formulations, administered twice-a-day (TD) and once-a-day (UP). In 20 asthmatic patients with low peak expiratory flow rate (PEF) in the morning (< 80% of predicted) administered TD (mean dose 475 mg/day) for 2 weeks, we evaluated PEF, diurnal variability of PEF, symptom score, results of spirometry and serum theophylline concentration (STC) and then changed theophylline, from TD to UP (mean dose 470 mg/day) for 2-4 weeks. PEF in the morning was higher during the UP period (mean +/- SD: 335 +/- 110 L/min) than during the TD period (mean +/- SD: 308 +/- 95 L/min) (p < 0.05), and diurnal variabirity of PEF was lower during the UP period (17.1 +/- 8.0%) than TD period (22.9 +/- 13.4%) (p < 0.05). However, there were no changes in PEF at night or daytime, symptom score, spirometry parameters or STC during the study period. The improvement in morning PEF observed in this study was consistent with the differences in pharmacokinetics between the two theophylline formulations. Morning PEF was increased during the UP period, probably because STC in the early morning during the UP period was higher than STC during the TD period.