It has been suggested that increase in delta sleep ratio (DSR), a marker for the relative distribution of slow wave activity (SWA) over night time, is associated with clinical response to antidepressant treatment. We examined this index and its relationship to rapid eye movement (REM) suppression before and during long-term treatment with nefazodone, which does not suppress REM sleep, and paroxetine which does. The effect of serotonin (5-HT2A) receptor blockade on the evolution of SWA during treatment was also investigated. In a double-blind, randomised, parallel group, 8-week study in 29 depressed patients, sleep electroencephalograms were performed at home at baseline, on night 3 and 10, and at 8 weeks of treatment with either paroxetine or nefazodone. SWA was automatically analysed and a modified DSR (mDSR) was derived, being the ratio of amount of SWA in the first 90 min of sleep to that in the second plus third 90-min periods. At baseline, the pattern of SWA over night time was similar to other reports of depressed patients. mDSR improved over the course of treatment; there was no difference between remitters and non-remitters but there was a significant drug effect and a significant drug × time effect with paroxetine patients having a much higher mDSR after treatment, regardless of clinical status. SWA and REM during antidepressant treatment appear to be interdependent and neither of them alone is likely to predict response to treatment. Higher mDSR did not predict therapeutic response. 5-HT2A blockade by nefazodone does not increase SWA above normal levels.