Antidepressants may have sleep and autonomic side-effects. The acute and long-term effect of reboxetine (2 mg b.i.d.) on sleep and cardiac autonomic activity was compared with that of placebo in a single-blind study. Twelve patients affected by dysthymia underwent four polysomnographic studies at baseline (placebo); at night 3 (reboxetine; acute effect); at night 9 (reboxetine; intermediate-term effect); and at night 122 (reboxetine; chronic effect). After the first administration, reboxetine increased time awake after sleep onset, number of awakenings, percentage of stages 1 and 2 non-rapid eye movement (REM), and reduced the amount of stages 3-4 non-REM, but all these effects disappeared by continuing treatment. However, reboxetine caused a persistent suppression of REM sleep, which was accompanied by an increase of REM sleep latency. The spectral analysis of heart rate variability showed a trend towards an increase in sympathetic activity with both acute and intermediate reboxetine use. Long-term treatment with 4 mg reboxetine does not cause significant changes in cardiac autonomic function.