The goal of our study was to examine the stability over time of the personality measures defined by Cloninger's Tridimensional Personality Questionnaire (TPQ) in patients with major depression. We conducted a retrospective chart review of 63 outpatients who had participated in one of three double-blind antidepressant trials. All subjects had completed the TPQ upon entry and upon termination of the 12-week trials. Statistically significant decrements in harm avoidance scores were observed in those subjects whose depression improved, regardless of gender or duration of presenting depressive episode. No significant changes were observed in the other two dimensions (novelty seeking and reward dependence). Nonresponders as a group had no statistically significant decreases in any TPQ dimension or subscales. While novelty seeking and reward dependence remain relatively independent of mood, harm avoidance appears to be a measure which is elevated during depressive states and which changes with improvement of depression. These findings are consistent with those of other investigators.