OBJECTIVES: To compare the sensitivity of the 6-item Hamilton Rating Scale for Depression (HRSD6) with the more widely used 17-item Hamilton Rating Scale for Depression (HRSD17) in patients suffering from major depressive disorder, with or without melancholia and/or dysthymic disorder. A secondary objective was to compare the sensitivity of the HRSD6 to the Montgomery-Asberg Depression Rating Scale (MADRS). DESIGN: Retrospective analysis of 4 clinical trials that tested antidepressant therapies. SETTING: Outpatient treatment in a major psychiatric hospital. PARTICIPANTS: One hundred and forty-three male and female outpatients meeting the criteria of the DSM-III-R or DSM-IV for major depressive disorder. OUTCOME MEASURES: HRSD17, HRSD6 and MADRS. RESULTS: The HRSD6 correlated strongly with the HRSD17, both at baseline and termination of treatment, and for the subgroups of double depression and melancholia. The HRSD6 was also correlated significantly with the MADRS at both measurement times, and for the subgroups. Paired t-tests with the HRSD6, HRSD17 and MADRS demonstrated equal sensitivity to change over the course of treatment, both in the full sample and in the dysthymic and melancholic subgroups. CONCLUSIONS: The HRSD6 appears to be as sensitive to change over treatment as the HRSD17 and the MADRS. A shorter, less time-consuming measure of depression may have utility in clinical practice and research.