Recent studies with clomipramine (CMI) have demonstrated that a pulse-loading approach is associated with a rapid improvement in symptomatology in the absence of continuous treatment. In the present study, sleep changes were evaluated to ascertain the rapidity of clomipramine's effect on electroencephalographic sleep, especially rapid eye movement (REM) and delta wave sleep measures. Clomipramine produced rapid changes in sleep with reduced sleep continuity and almost complete suppression of REM sleep as well as a redistribution of slow wave sleep. Delta waves during sleep were also found to be shifted to the earlier part of the night and increased in intensity. Spectral analysis revealed an increase in power in the delta frequency range that was correlated with clinical responsiveness. These studies point toward a role for clomipramine in the rapid treatment of depression and confirm that sleep physiology may be a good predictor of antidepressant action.