The effects of once a day dose of sulpiride efficacy and safety was evaluated in patients with major depressive disorder. The patients received sulpiride once a day in the morning or in the evening. There were no significant differences between two groups in the mean measures of efficacy. Side effects were rare and all of a mild degree. The most common side effects were sedation, constipation, and dryness of mouth. Out of regard for the administrative and psychological advantage of the once a day dosage this form should be preferred in the treatment of major depression.