Lymphocytes from human peripheral blood exhibit a series of markers of neurotransmitters, such as specific receptors and transporters. A reduction of serotonin transporters and an increase of them has been reported after treatment with fluoxetine in depressed patients. The aim of this study was to determine if the administration of an antidepressant with a different mechanism of action, such as mirtazapine, could produce a similar effect. Twenty eight patients (age 41.40+/-2.45) were diagnosed following the criteria for major depression by the Structured Clinical Interview for Disorders of Axis I of the American Psychiatric Association. Severity was measured by Hamilton Scale and by Beck Inventory for Depression, scores of 30.88+/-7.48 and 30.24+/-10.88, respectively, prior to treatment. Samples from control subjects were obtained alternating with patients before and after the administration of the antidepressant: twenty eight and twenty four, respectively (age 38.80+/-2.95). Mirtazapine was given in a dose of 30 mg/day for 6 weeks. Blood lymphocytes were isolated by density gradient from patients and controls before and after treatment. There was a partial response according to clinical evaluation and scores of the Scale and the Inventory. Serotonin transporters were labeled with [3H] paroxetine. Number of sites (B(max)) were 10.86+/-2.60 and 12.58+/-2.71 fmol/10(6) cells for both groups of controls. The depressed patients had a significant reduction of serotonin transporters in their lymphocytes before treatment and an increase after it, with B(max) values of 6.52+/-0.49 and 15.61+/-0.49 fmol/10(6) cells, respectively. There were no significant differences in the affinity for the ligand. Concentrations of serotonin or noradrenaline in lymphocytes were not modified before the treatment, although there was a significant decrease after taking 30 mg/day of the antidepressant for 6 weeks. Mirtazapine, not being a serotonin reuptake inhibitor, did increase the number of transporters in lymphocytes of major depression patients, indicating a complex mechanism, not only directly related to the transporter, but involved in the therapeutic response.