The objective of this study was to assess whether treatment with sustained-release bupropion (Wellbutrin-SR) produces alterations in electroencephalographic (EEG) sleep that are associated with clinical response to the drug. EEG sleep was measured in 20 patients with unipolar major depressive disorder before and after treatment with sustained-release bupropion. Each EEG sleep session consisted of two consecutive nights. Treatment with bupropion lasted for 8 wk. Compared to EEG sleep measures at baseline, treatment with bupropion significantly lengthened REM latency, increased REM activity and density during the first REM period, and increased total REM density. Differential response to treatment was associated with changes in REM activity and density, but not with REM latency. However, in contrast to many other antidepressants, REM sleep was not suppressed.