We examined the risk of attempted suicide in 100 inpatients during a major depressive episode. We hypothesized that patients who attempt suicide have a vulnerability for suicidal behavior independent of severity or duration of depression, manifested by suicide attempts early in the course of a depressive episode. The first 3 months after the onset of an MDE and the first 5 years after the lifetime onset of major depressive disorder represented the highest-risk period for attempted suicide, independent of the severity or duration of depression. Familial, genetic, early-life loss experiences and comorbid alcoholism may be causal factors.