Objective: The authors' goal was to examine the hypnotic effects of slow-release melatonin during the initial 4 weeks of treatment with fluoxetine in 19 patients with major depressive disorder. Method: Twenty- four outpatients with major depressive disorder were included in the study; 19 completed the study. Ten patients were treated with fluoxetine plus slow- release melatonin and nine were given fluoxetine plus placebo in a double- blind protocol for 4 weeks. Response was assessed by using rating scales for depression and sleep. Results: The 10 patients given slow-release melatonin reported significantly better scores on the Pittsburgh Sleep Quality Index than the nine patients given placebo. No significant differences in the rate of improvement in depressive symptoms were noted between the two groups. No particular side effects were noted from the combination of fluoxetine and slow-release melatonin. Conclusions: Slow-release melatonin was effective in improving the sleep of patients with major depressive disorder. Slow-release melatonin had no effect on the rate of improvement in symptoms of major depressive disorder. The authors conclude that the role of slow-release melatonin for sleep disturbances in major depressive disorder should be investigated further.