To study the short-term effects of theophylline on sleep and wakefulness, 24 healthy men and women, aged 21 to 35 years, received each of three doses, 0, 3, and 6 mg/kg, of theophylline double-blind in a Latin Square design, administered to 12 subjects at 9 AM and to the other 12 at 11 PM. After the daytime administration, sleep latency was tested at 10 AM, 12 Noon, 2 PM, and 4 PM and divided attention and auditory vigilance performance were tested at 10:30 AM and 2:30 PM. After the nighttime administration, a standard 8-h polysomnogram was collected. On a separate day all subjects received a single 6-mg/kg dose at 9 AM and blood samples were drawn at 8:30 and 10:30 AM, 12:30 PM, 2:30 PM, and 4:30 PM. The serum theophylline levels for the 6-mg/kg dose peaked at 11.0 micrograms/mL and declined to 8.1 micrograms/mL by 4:30 PM. In the daytime administration, daytime mean sleep latency was increased by both doses and performance was improved by the high dose but not the low dose. In the nighttime administration, nocturnal sleep onset was delayed and total wake time was increased by the high dose but not the low dose. The low dose increased the amount of light stage 1 sleep without producing wakefulness.