Unipolar depression is frequently a recurrent or chronic disorder. In studies on predicting its course, outcomes are typically linked to either psychiatric features or stressful life events. In order to integrate the 2 approaches, 51 unipolar patients were assessed periodically over at least 1 year for symptoms, stressful events, and chronic stressors. It was hypothesized that adverse family history and early age of onset impair role functioning and coping capabilities, thereby contributing to stressful circumstances that predict severity of depressive reactions. Results of causal modeling analyses supported a model in which background factors were associated with severity of depressive outcomes as mediated by their effects on stress variables. Such a model implicates the self-perpetuating nature of clinical depression, both for the individual and across generations.