Study aim. To develop a highly sensitive method for assaying platelet serotonin concentrations suitable for use in daily clinical practice. Materials and methods. The method was intended for assay of platelet-enriched plasma (PEP). Serotonin was assayed by high performance liquid chromatography (HPLC) with fluorimetric detection and a hematology analyzer. Results and discussion. Investigations of healthy subjects yielded platelet serotonin concentrations consistent with published data: from 2.19 to 4.87 nmol/109 platelets. Investigations of 30 patients with depressive disorders identified decreased platelet serotonin concentrations, with levels ranging from 0.11 to 2.89 nmol/109 platelets, along with a correlation between this value and clinical evaluation of the severity of depression. The authors regard the method developed here as suitable for clinical purposes.