OBJECTIVE: Depressed patients often experience interpersonal distress. Understanding how interpersonal distress and depressive symptoms are associated may have implications for understanding the etiology and maintenance of depression, as well as for treatment. In this naturalistic psychotherapy study, we explored whether change in depressive symptoms predicted subsequent change in interpersonal distress or vice versa. METHOD: Depressive symptoms (depression scale of the Symptom Check List-90-Revised) and interpersonal problems (Inventory of Interpersonal Problems-64) were assessed on nine occasions, including before, during, and after treatment and at 1 and 2.5 years follow-up in a sample of 178 depressed patients receiving open-ended psychotherapy. We used latent curve modeling with structured residuals to assess possible reciprocal relations between interpersonal problems and depression, controlling for personality disorder. RESULTS: The findings showed that interpersonal distress had a slower rate of change compared to depressive symptoms, but improvements in interpersonal distress predicted subsequent improvement in depressive symptoms during psychotherapy, and this effect was stable over time. Patients with comorbid personality disorder had higher initial levels of both depression and interpersonal distress, but there were no differences in rates of change for any of the outcomes. CONCLUSION: Our results indicate that improvements in interpersonal problems may play an important role in alleviating depressive symptoms during psychotherapy. We propose that reduction of interpersonal distress is associated with increased interpersonal flexibility, which may lead to more positive responses from others, thereby contributing to a reduction in depressive symptoms. (PsycInfo Database Record (c) 2025 APA, all rights reserved).