In general, depressed patients with personality pathology--Axis II disorders--respond less well or less quickly to the various kinds of individual treatment that are available, whether pharmacotherapy, psychotherapy, or both combined. This article sets forth the results of a six-month, randomized clinical trial of antidepressants and combined therapy in ambulatory patients with major depression and a baseline score of at least 14 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17). The presence or absence of Axis II pathology was determined on the basis of a self-report version of the International Personality Disorder Examination. The study's antidepressant protocol provided for three successive steps in case of intolerance or inefficacy: fluoxetine, amitriptyline, and moclobemide. In addition to pharmacotherapy, the combined-therapy condition included 16 sessions of Short Psychodynamic Supportive Psychotherapy. Efficacy of the therapy provided was assessed using the HAM-D-17 and also other instruments. According to the results in secondary analyses, it emerged that combined therapy was more effective than pharmacotherapy for depressed patients with personality disorders. Combined therapy was not more effective than pharmacotherapy alone for depressed patients without personality disorders. It is recommended that depressed patients with comorbid personality pathology should be treated with combined therapy, with the focus of psychotherapy being not on the patient's symptoms and complaints, but on all aspects of the patient's actual relationships.