Circadian alterations in lung function occur in respiratory disorders, with the nadir during the sleep-related hours. Higher therapeutic serum theophylline concentrations (STC) during the night have been shown to improve lung function in reversible airway disease. To determine what effect higher nocturnal STC would have in patients with chronic obstructive pulmonary disease (COPD) on overnight lung function, oxygen saturation, and sleep quality, two different theophylline products were used to give higher or lower STC during the night. We found that with a higher STC (15.0 +/- 1.0 versus 11.0 +/- 1.0 micrograms/ml, p = 0.005) at 7:00 A.M., the overnight changes in FEV1 (+7.4 +/- 5.7% versus -18.9 +/- 7.9%, respectively) and FVC (+1.8 +/- 7.5% versus -17.2 +/- 3.9%, respectively) were significantly better. However, there was no apparent effect on oxygen saturation (mean sleep values for higher STC were 85.3 +/- 1.2%, and for lower STC they were 86.5 +/- 0.8%). The higher STC did not adversely affect sleep latency, sleep efficiency, or sleep staging. We conclude that a higher therapeutic STC during sleep will improve lung function without altering oxygen saturation in patients with COPD. In this group of patients, the higher STC did not interfere with sleep characteristics.