Five endogenous depressed patients were asked to participate in a phase-shift experiment consisting of advancing, by 5 hours, the time-schedule of the major external synchronizers such as light/dark cycle, sleep/wake, meal-time and social activity cycles. Clinical and biological parameters (body temperature, plasma cortisol, TSH and norepinephrine (NE) circadian rhythms) were observed throughout this two week period. The circadian rhythms were severely altered in the pre-treatment period, with a significant reduction of amplitude. During the phase shift experiment, the clinical state of the patients improved significantly. Their circadian rhythms were dramatically impaired in the first days of the procedure and were then restored after the first week, with higher amplitude. However, the TSH circadian rhythm remained unentrained by the phase shift leading to an internal desynchronization. Our findings suggest that entrainment of internal clocks by environmental information may be impaired in depression.