We measured the rate of aqueous flow and analysed its relation to the time of day, the state of wakefulness and the urinary excretion of catecholamines. Two groups of subjects were studied. One group comprised 20 normal subjects who were studied over two 22-hr periods. During one period, the subjects were permitted to sleep during their customary hours of sleep; during the other, they were not permitted to sleep, but remained active for all 22 hr. The other group comprised ten subjects with obstructive sleep apnea who were studied over a 22-hr period and slept during their customary hours of sleep but without the aid of any respiratory device. Aqueous flow was measured with fluorophotometry. Motion of the wrist was monitored by a seismograph (wrist Actigraph) and served as a surrogate of activity and wakefulness. Urinary catecholamine excretion was measured during different periods of the wake/sleep cycle. Both groups exhibited the normal nocturnal suppression of flow (59% lower compared to morning in the normal group; 56% lower compared to morning in the apneic group). During sleep deprivation, the rate of flow at night in normal subjects was 30% lower than during the morning (P < 0.001) and 60% higher than during sleep (P < 0.001). Lid closure during sleep deprivation had no effect on the results. Aqueous flow correlated with a 'catecholamine index', derived from the combined excretion of epinephrine and norepinephrine. Flow also correlated with an 'activity index', and 'sleep efficiency', indices derived from motion of the wrist. We conclude that the day-night difference of aqueous humor flow as measured by clearance of fluorescein from the human eye is driven partly by a factor that has a circadian rhythm and partly by a factor that depends on the activity of the subject. We hypothesize that these factors are the catecholamines, epinephrine and norepinephrine.