In order to study effects of theophylline on sleep, a randomised double-blind cross-over study with slow release theophylline vs. placebo was performed on 13 healthy male volunteers (mean age 24 years), eight of whom were considered caffeine-sensitive and five caffeine-insensitive. A sleep diary was filled in during the entire period. At the end of each 2 week study period a sleep questionnaire was filled in and a sleep recording was conducted. Seven of the eight caffeine-sensitive persons reported that their sleep was disturbed during the theophylline period, while none of the five caffeine-insensitive experienced any difference between the periods. Analysis of the sleep diaries (mean +/- SD) revealed a significant increase in sleep latency (16 +/- 11 vs 4 +/- 7 min) and decrease in sleep efficiency (95 +/- 3 vs 98 +/- 3%) among the caffeine-sensitive persons during the theophylline period compared with the placebo period, while no such difference was found among the caffeine-insensitive. We conclude that theophylline seems to disturb sleep mainly in caffeine-sensitive persons.