Patients with Huntington's disease (HD) often suffer from psychiatric symptoms including affective disorder, psychosis, irritability, and apathy, which may be present in all stages of the disease. However--despite the obvious likelihood that these symptoms may be reduced by antidepressive treatments--to date, the effectiveness of such treatments in HD has only ever been examined in case studies. Twenty-six HD patients (17 men), with a diagnosis of major depression, were studied. The symptoms of HD and depression were systematically measured using the Beck Depression Inventory and the Hamilton Rating Scale for Depression both at baseline and after 4 weeks of treatment with venlafaxine XR. After 4 weeks of venlafaxine XR treatment, the symptoms of depression in HD patients decreased significantly relative to baseline. However, approximately one in five patients developed significant venlafaxine-related side effects (nausea and irritability). Venlafaxine XR is highly effective in the treatment of depression in HD, although it may produce unpleasant side effects. Further studies are required to establish the most suitable treatment for depression in HD.