Recent European studies suggested that sleep phase advance (SPA) could sustain the effects of total sleep deprivation (TSD) both with or without a combined antidepressant drug treatment. Previous studies by our group showed that an ongoing lithium treatment could enhance and sustain the effect of repeated TSD. In the present study we studied the effect of a single TSD followed by 3 days SPA (beginning with sleep allowed from 17:00 until 24:00, with daily shiftbacks of 2 h) in consecutively admitted bipolar depressed inpatients who were taking a chronic lithium salts treatment (n=16) or who were devoid of psychotropic medications (n=14). Changes in mood during treatment were recorded with self administered visual analogue scales and with Hamilton rating scale for depression. Results showed that SPA could sustain the acute antidepressant effect of TSD, and that lithium enhanced the effect of the chronobiological treatment. According to the internal coincidence model, the better clinical effects observed in lithium-treated patients could be due to the phase delaying effect of lithium on biological rhythms, leading to a better synchronization of biological rhythms with the sleep-wake cycle.