Background: Neuroimaging, immunologic, and pharmacologic studies have emphasized the role of 5-HT2A and 5-HT3A serotonin receptors in the pathophysiology of major depression.Aim: The aim of this study was to measure the relative expression of 5-HT2A and 5-HT3A receptor mRNA in peripheral blood mononuclear cells (PBMCs) of patients with major depressive disorder (MDD).Method: 5-HT2A and 5-HT3A receptor mRNA expressions were examined in PBMCs of 25 medication-naive-patients with MDD, 25 medication-free MDD patients, and 25 healthy controls. 5-HT2A and 5-HT3A receptor mRNA expressions were measured using real-time quantitative PCR. This study evaluated patients' clinical symptoms using the Hamilton Depression Rating Scale-17 items (HDRS) and the Beck Depression Inventory (BDI).Results: Relative 5-HTR2A mRNA expression was significantly higher in PBMCs of all MDD patients when compared with healthy controls (Z = -3.875, p0.05). MDD patients showed significant correlations between 5-HTR2A mRNA expression and HDRS scores (rs=0.902, p<0.001) and BDI scores (rs=0.878, p<0.001).Conclusion: This study showed that depressed patients, irrespective of treatment, have higher 5-HTR2A mRNA levels in PBMCs than healthy subjects. It also provided evidence that 5-HTR2A mRNA levels in PBMCs of MDD patients could be associated with the severity of depression and the duration of the illness.