Objective: Patients with chronic fatigue syndrome complain of unrefreshing sleep, and some have poor sleep indicative of sleep disruption. We hypothesized that some CFS patients had a disorder of arousal which interfered with normal sleep which would manifest itself by difficulty falling asleep after a night of sleep deprivation. To test this, we determined sleep latency after a night of sleep deprivation. Methods: Patients and healthy controls, previously habituated to sleeping in a sleep lab, returned for a normal night of sleep and for a night of sleep deprivation followed by determination of latency to fall asleep. Patients also had indwelling catheters to allow repeated sampling of plasma for cortisol, a hormone whose levels might reflect arousal. Results: Five of 15 patients showed delays in falling asleep, relative to the healthy controls. Sleep latency following sleep deprivation correlated inversely with sleep efficiency on the normal sleep night. No significant difference was found in cortisol patterns across time for patients and controls on the sleep deprivation night. However, the slope of the curve was shifted up significantly for patients but not for controls on the normal sleep night. Conclusion: A subgroup of patients has difficulty falling asleep after a night of sleep deprivation. These patients may have a disorder of arousal that interferes with their having normal sleep. CFS patients as a group show a shift upwards in the temporal pattern of cortisol during the night a possible measure of their being stressed while sleeping.