OBJECTIVE To determine if there are significant differences in the temporal organization of rapid eye movement (REM) sleep microarchitecture between healthy controls and outpatients with major depressive disorder (MDD). METHODS Forty age-matched subjects, 20 men and 20 women, half with MDD, were selected from an archive of sleep electroencephalography (EEG) data collected under identical conditions. Each participant spent 2 consecutive nights in the Sleep Study Unit of the University of Texas Southwestern Medical Center at Dallas, the first of which served as adaptation. The average amplitude in each of 5 conventional EEG frequency bands was computed for each REM period across the second night. Data were then coded for group and sex. RESULTS Aside from REM latency, none of the key sleep macroarchitectural variables differentiated MDD patients from controls. REM latency was longest in men with MDD. Sleep microarchitecture, however, did show a number of between-group differences. In general, slower frequencies declined across REM periods, with a significant REM period effect for delta, theta and alpha amplitude. Group x sex interactions were also obtained for theta and alpha. Beta activity showed a unique temporal profile in each group, supported by a significant REM period x group x sex interaction. In addition, the temporal change in theta amplitude across REM periods was most striking in women with MDD. CONCLUSIONS This study suggests that, like during non-REM sleep, EEG amplitude shows a systematic temporal change over successive REM sleep periods and also shows elements that are both disease- and sex-dependent.