Do total sleep deprivation and sleep-wake rhythm manipulations trigger remission from the depressive episode, or do they cause only transient positive mood fluctuations? Several nonpharmacologic strategies have been proposed to sustain the effect of total sleep deprivation, and simple serial repetition of total sleep deprivation prevents short-term relapse among drug-free depressed patients (R1558282E). In agreement with the literature (R1558283E), however, we observed a subsequent relapse among unmedicated patients after a variable delay. Moreover, total sleep deprivation has been shown both to hasten the antidepressant action of fluoxetine in previously unmedicated patients (R1558284E) and to trigger a sustained response in fluoxetine nonresponders (R1558285E). Similar effects could have occurred with unmedicated patients and nonresponders to amitriptyline, and differences between groups might have been revealed later in the course of the depressive episode.