In the present study patients with a major depressive disorder were first subjected to total sleep deprivation (TSD) and then treated with clomipramine. Sleep electroencephalography (EEG) was registered prior to and after TSD, during the 2 initial nights of antidepressive treatment and after 19 days. A negative correlation between response to TSD and clomipramine was found. TSD did not differentially influence the sleep EEG (responders vs nonresponders): responders tended, however, to show a more classical depressive sleep pattern prior to TSD. Clomipramine profoundly suppressed rapid eye movement (REM) sleep; the amount of initial REM sleep reduction, however, did not correlate significantly with therapy response after 3 weeks of treatment.