Aim. Genetically determined activity of CYP2D6 may be modified by some drugs through inhibition processes. Inhibition properties of TCA's were confirmed mainly in in vitro Studies. The aim of the study was to assess the influence of clomipramine on CYP2D6 activity in vivo. Method. 11 patients diagnosed with depression according to ICD-10 and DSM-IV (major depression) criteria were included in the study. In all the cases clomipramine therapy was indicated. CYP2D6 activity was assessed by the phenotyping method. All patients were treated simultaneously. Each of the patients ingested one tablet containing 100 mg of sparteine sulfate. Urine excreted during the following 6 h was collected. Based on sparteine metabolic ratio (MR) the phenotype status was estimated twice: after the wash-out period, before clomipramine treatment, sparteine metabolic ratio (MR1), and after 2-weeks of clomipramine treatment (MR2). Results. During clomipramine treatment MR2 values were statistically significantly higher than MR1. In 3 patients (27.3%) treated with clomipramine the changes of phenotype status were observed. Conclusions. Clomipramine is a CYP2D6 inhibitor and may change the CYP2D6 phenotype status (EM into PM).