We compared the effects of evening administration of sustained-release theophylline (Uniphyl) and qid inhaled beta 2-agonist (salbutamol, two 100-micrograms puffs) on sleep quality and nocturnal oxygen saturation in 20 patients with COPD. Patients with FEV1 less than 70% predicted and FEV1/FVC ratio less than 70% were eligible to participate in this double-blind, crossover study, with 2-week treatment arms. Patients recorded morning and evening peak flow and symptoms in a daily diary. On the last day of each treatment period, overnight polysomnography was done. Spirometric indexes were measured before retiring and on awakening. Patients spent less time at less than 90% oxygen saturation (51 +/- 92 min vs 72 +/- 105 min; p = 0.03) during theophylline treatments than during salbutamol treatment. There was a smaller overnight decrease in FEV1 (0.04 L vs 0.13 L; p = 0.04) after theophylline than after sallbutamol treatment. FEV1/FVC ratio and maximum expiratory flow at 50% of vital capacity (V50) increased overnight with theophylline and decreased with salbutamol (p = 0.014, 0.025). Morning peak expiratory flow rate was higher with theophylline (4.0 +/- 1.7 L/s) than with salbutamol (3.6 +/- 1.8 L/s; p = 0.004). The duration of patient-reported nocturnal wheezing was lower with theophylline than with salbutamol (p = 0.006). There were no differences between treatments in sleep quantity, efficiency, staging, or subjective quality. We conclude that, compared with salbutamol, evening administration of once-daily theophylline results in better nocturnal oxygen saturation and an improvement in the overnight change in pulmonary function, without affecting sleep architecture, in patients with COPD.