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Within the framework of interpersonal and cognitive theories of depression, we investigated whether the perception of facial emotions was associated with subsequent relapse into depression. The 23 inpatients with major depression who remitted (65 admitted patients) were studied at admission (T0), at discharge (T1), and 6 months thereafter to assess relapse. They judged schematic faces with respect to the expression of positive and negative emotions. Six patients (26.1%) relapsed. High levels of perception of negative emotions in faces, either assessed at T0 or at T1, were associated with relapse. Moreover, subjects saw more negative emotions in depressed than in remitted state. Significant results were confined to ambiguous faces, i.e., faces expressing equal amounts of positive and negative emotions. Our data support the hypothesis that a bias toward the perception of others' facial emotions as negative is an enduring vulnerability factor to depression relapse and depressed mood amplifies this negative bias in perception.