The distribution of slow-wave activity during sleep has been analyzed using a method related to the two-process model of sleep regulation. This method is applied to the analyses of data collected from 21 inpatients with unipolar depression who received the antidepressant clomipramine (CMI) in a pulse-loading protocol. CMI infusion was found to redistribute slow-wave activity, producing more concentration in the early part of the night, and also significantly reduced the fluctuation in slow-wave power as a function of time. These measures also distinguished clinical responders from the nonresponders. Drug responders had a significant redistribution of slow-wave activity to the earlier part of the night as compared to nonresponders. This suggests that measures of the distribution of slow-wave activity over the night may represent a good measure of clinical response to antidepressant therapy and have implications for the interpretation of the two-process model and sleep in depression.