This study investigates whether response to total sleep deprivation in depressed patients may be predicted by the presence of diurnal variation of mood. Diurnal variation was measured with two different self-rating scales in 140 untreated depressed patients. Sleep deprivation responders manifest a higher percentage of diurnal variation than nonresponders, with a pattern of improved mood in the evening. Patients with marked diurnal variation respond better to sleep deprivation than those with little. The symptom of diurnal variation is a potential marker for a patient's likelihood to respond to different therapies.