Background. A limited number of psychotherapy sessions in combination with medication is preferable to pharmacotherapy only in the treatment of ambulatory patients with major depression. Whether there is a relation between the number of sessions and the efficacy of the treatment is uncertain. Method. Randomized clinical trial comparing two treatment conditions in outpatients with major depression. All patients studied had a baseline score of at least 14 points on the 17-item Hamilton Depression Rating Scale. The two conditions consist of 8-session or 16-session Short Psychodynamic Supportive Psychotherapy, both in combination with pharmacotherapy. Efficacy was assessed using the 17-item HDRS, the CGI of Severity and of Improvement, the depression subscale of the SCL-90 and the Quality of Life Depression Scale. Results. The rate of change would seem to indicate that eight sessions are preferable for both moderately and severely depressed patients, although the results converged again at the end. Furthermore, in terms of satisfaction with the number of sessions and drop-out percentages during treatment, no differences were found between the conditions. Conclusion. In the light of the outcome analysis (faster remission after fewer sessions), a short version of the psychotherapy treatment in a combined course of treatment seems to be justified. © 2004 Cambridge University Press.