Background: We have previously reported that severe depression is associated with immunological and inflammatory alterations and these alterations may be showed easily by polymorphonuclear elastase (PMNE) measurements. The purpose of the present study is to show how PMN elastase levels change before and after antidepressant treatment. Methods: Fifty-five patients with depression (40 with major depression [MD], 15 with dysthymic disorder [DD]) were included in the study. Blood samples were drawn prior to drug treatment, and 3 months after the treatment. Severity of depression was measured by 24-item Hamilton depression rating scale (HDRS). Results: There was a positive correlation between Delta PMNE levels and Delta HDRS in patients with MD, but not in patients with DD. Twenty-eight patients were given moclobemide, and 27 patients were given imipramine. It was seen that PMN elastase levels were significantly reduced after 3-month antidepressant treatment period only in patients with MD. Conclusion: These findings suggest that PMNE activity is a state dependent parameter and improvement of depressive symptoms due to antidepressant treatment may lead to decrement of PMNE levels. Clinical implication and limitations: PMN elastase measurements may be used as a sensitive biological marker to follow the time-course of the disease activity in patients with major depression. (C) 2000 Elsevier Science B.V. All rights reserved.