The effect of theophylline on sleep quality and cognitive performance in patients with obstructive lung disease has been the subject of controversy. To examine the direct effects of theophylline on sleep quality and cognitive performance, without confounding effects from bronchodilatation, we have undertaken a study of the drug in healthy subjects. A double-blind, placebo-controlled crossover protocol was used to study the effect of oral sustained-release theophylline (Theodur) on subjective sleep quality, objective sleep quality, and cognitive performance. Overnight sleep studies were carried out on Nights 13 and 14 of each 2-wk study limb, and cognitive performance tests administered on Days 1 and 13 of each limb. A total of 18 subjects satisfactorily completed the study (8 males, median age 37, range 24 to 67 yr). Theophylline levels were median 10.2, range 2.3 to 13.3 micrograms/ml on Day 1 and 14.7, range 9.6 to 17.5 micrograms/ml on Day 13. No significant difference was observed between theophylline and placebo on subjective or objective sleep quality or on acute or medium-term cognitive performance. We conclude that theophylline does not affect sleep quality or cognitive performance in normal adults.