Objectives: To investigate the biological factors related to the onset of Bell's palsy, we sought to identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) and plasma of patients with Bell's palsy and Ramsay Hunt syndrome (RHS). Methods: We carried out DNA microarray analyses using PBMCs taken from patients with Bell's palsy at their initial visit and 2 to 4 weeks later. To validate these analyses, we measured the relative messenger RNA levels of α-defensin in paired PBMCs by reverse transcription–polymerase chain reaction. The plasma concentrations of α-defensin in patients and healthy volunteers were quantified by enzyme-linked immunosorbent assay. Results: The DNA microarray analysis identified α-defensin as a candidate gene related to the onset of Bell's palsy. Reverse transcription–polymerase chain reaction analysis showed that the relative α-defensin messenger RNA levels in PBMCs from the later visit were increased at least twofold in 9 of 13 patients (69%) with Bell's palsy and in 4 of 6 patients (67%) with RHS. The plasma α-defensin concentrations in the patients with RHS were significantly higher than those in healthy volunteers (p = 0.0013) and in the patients with Bell's palsy (p = 0.0306). Elevations of plasma α-defensin were observed in 5 of the 9 patients with Bell's palsy who demonstrated α-defensin overexpression in PBMCs. Conclusions: α-Defensin may be one of the biological factors related to the onset of Bell's palsy and RHS.