This study examined whether reactance would negatively influence treatment outcome in 347 patients diagnosed with chronic forms of depression and treated at 9 sites with either Nefazodone, cognitive-behavioral analysis system of psychotherapy (CBASP), or combination therapy. Contrary to our hypotheses, reactance positively predicted treatment outcome in CBASP on 2 of 4 scales. These effects were independent of the therapeutic alliance, which also positively predicted outcome. Reactance did not predict outcome in the groups receiving medication alone or in combination with CBASP. The findings suggest that reactance may be an asset in psychotherapy among chronically depressed individuals and that reactant patients can benefit from directive psychotherapy when therapists flexibly respond to perturbations in the therapeutic relationship. Results support the importance of Aptitude * Treatment interactions in psychotherapy outcome. The direction and significance of such interactions may vary with different forms of psychopathology.