Many patients continue to experience depressive symptoms after optimal pharmacological treatment. The aim of this study was to investigate whether Beck's cognitive diathesis stress model of depression would help predict the degree of improvement in the depressive symptoms of patients with chronic depression receiving antidepressant treatment. The study investigated the dysfunctional attitudes, perceived stress, and depressive symptoms of 117 patients with chronic depression before and after they were treated with an 8-week course of fluoxetine. A hierarchical multiple regression analysis showed a significant effect for the interaction between dysfunctional attitudes and perceived stress explaining severity of depressive symptom following antidepressant treatment. Patients with both high perceived stress and high dysfunctional attitudes prior to treatment reported more depressive symptoms at the end of treatment than patients with high perceived stress and lower dysfunctional attitudes. Surprisingly, in the presence of low perceived stress, patients with higher dysfunctional attitudes experienced less depressive symptoms at the end of treatment than patients with lower dysfunctional attitudes. Results suggest the value of taking into consideration both patients' perceived stress and dysfunctional attitudes when assessing treatment for depressive symptoms.