The amplitude and time course of slow-wave activity (SWA) during NREM sleep were compared in 76 outpatients with depression and 55 healthy control subjects. Lower SWA amplitude was evident in the depressed group, especially among depressed men. For the most part, significant differences between patients and control subjects were restricted to the first NREM period and only in those 20-30 years of age. Significant age-related declines in SWA amplitude were evident in control subjects but not in depressed patients. In addition, sex differences in the depressed group were twice as large as those seen in control subjects. The time course of SWA amplitude, presumed to reflect homeostatic sleep regulation of SWA, was only abnormal in depressed men with lower accumulation and slower dissipation over NREM sleep. Depressed women showed no evidence of an abnormal SWA time course. Furthermore, no sex differences in the time course of SWA were evident in control subjects, and age-related changes in this aspect of regulation were not striking in any group. Thus, the amplitude of SWA showed strong age effects in healthy individuals but not in those with MDD whereas the time course showed very subtle age effects. It was suggested that men, but not women, with MDD show impaired SWA regulation that is evident from 20 to 40 years of age. These findings provide further support that the pathophysiology of depression differs for men and women and suggest that maturational effects on SWA in depression differ from those observed in healthy individuals.