The aim of the present study was to evaluate the pattern of basal cortisol release in PTSD and major depression using a chronobiological analysis. Plasma for cortisol determination was obtained from 15 combat veterans with PTSD, 14 subjects with major depression, and 15 normal men every 30 min during a 24-hour period of bed rest. Raw cortisol data were modeled using standard and multioscillator cosinor models to determine the best fitting functions for circadian, hemicircadian, and ultradian components of cortisol release. PTSD subjects had substantially lower cortisol levels, and displayed a pattern of cortisol release that was better modeled by circadian rhythm. PTSD subjects also showed a greater circadian signal-to-noise ratio than the other groups. In contrast, depressed patients displayed a less-rhythmic, more chaotic pattern of cortisol release. The pattern of cortisol secretion and regulation observed in the PTSD group under baseline conditions may reflect an exaggerated sensitization, whereas the chronobiological alterations in depression may reflect dysregulation, of the hypothalamic-pituitary-adrenal (HPA) axis.