A comprehensive study of circadian rhythms was carried out in 16 drug-free patients with endogenous depression, 10 of whom were reinvestigated after clinical remission, and 10 healthy controls. No free-running periods were observed in body temperature, urinary excretion of potassium and free cortisol, or any other variable. Moreover, there was little, if any, indication of phase-advance. The circadian variation of several variables was reduced during depression, e.g., motor activity, body temperature, and (less markedly) urinary potassium, but not cortisol. The circadian worsening of mood tended to occur around the time of awakening during depression, i.e., several hours later than after remission or in normal controls. In patients with circadian variation of self-rated mood, the acrophase of this variable correlated significantly with that of urinary free cortisol. This indicates an entrainment of the disease process to the circadian rhythm of cortisol secretion, probably via circadian variations of neurotransmitters in the hypothalamus. The other circadian phenomena observed in depression can adequately be explained by masking effects (negative or positive) of psychopathological symptoms (e.g., early morning awakening) on overt circadian rhythms.