This report documents cases of suicide attempts by two persons with Down's syndrome. The patients experienced dysphoric affect and feelings of hopelessness about unmet needs associated with their disability. During the course of a major depressive episode, each individual made a suicide attempt that could have been fatal. Although suicidal ideation and attempts are infrequent among patients with mental retardation, completed suicides and potentially fatal attempts have been reported. It is vitally important that mental health practitioners appreciate the seriousness of suicidal ideation among persons who have mental retardation and treat the underlying psychiatric disorder.