In our previous study of partial sleep deprivation (PSD), we considered both the timing of sleep and the duration of sleep as potential factors in determining response to treatment (annual report Z01 MH 0221-02 CP). We found that the clinical response to sleep deprivation was proportional to the reduction in sleep, and in particular REM sleep. The timing of sleep also appeared to be a factor with patients showing significantly greater improvement when sleep deprived in the second half of the night (PSD-L) than in the first half of the night (PSD-E). The effect of timing on the PSD response was confounded by the fact that patients sleep significantly less on the PSD-L condition. An additional finding of this study was that the antidepressant response to a single night of PSD could be extended by repeating the procedure for a second night. In our present study, we are comparing the relative effects of PSD-L and PSD-E with the duration of sleep rigidly controlled. In a second study, we are assessing the cumulative antidepressant efficacy of PSD performed over a three week period. Six subjects have been studies to date. Our data is not sufficient to determine the relative efficacy of the two treatments but we have succeeded in achieving comparable sleep reductions on the two treatments. In the longitudinal study of PSD, two patients improved, one with complete remission of her depression, and four showing essentially no change with treatment. A larger sample will be required to establish whether PSD has sustained antidepressant effects in depression.