Background: Antimicrobial peptides (AMPs) are small molecular weightproteins with broad spectrum antimicrobial activity against bacteria,viruses, and fungi. Cathelicidins and defensins are major groups ofepidermal AMPs. In addition to important antimicrobial properties,growing evidence indicates that AMPs alter the host immune responsethrough receptor-dependent interactions. Antimicrobial peptides havebeen shown to be important in such diverse functions as angiogenesis,wound healing, and chemotaxis. As our knowledge of AMP biologyexpands, the precise role and relevance of these peptides will be betterelucidatedAim of work: The aim of this study is to evaluate and compare thepossible role of Human Beta Defensin-3 (HBD-3) in the pathogenesis ofdifferent clinical types of viral warts.Patients and Methods: The study included 60 patients arriving to theDermatology clinic, Faculty of Medicine, Cairo University and diagnosedclinically with cutaneous warts. The study also included 20 age and sexmatched healthy controls. Patients were divided into three groups, eachcomposed of 20 patients, Group A: patients with common warts, GroupB: patients with plane warts and Group C: patients with plantar warts . Ablood sample (5ml) was taken from each patient and control subject andthen subjected to enzyme linked immunosorbant assay (ELISA) forestimation of HBD3.The ELISA results of HBD3 were then statisticallyanalyzed and compared among the three groups.Results: The results of HBD-3 in 3 groups against controls showed thatHBD-3 was highly elevated in the sera of patients with warts comparedwith controls(P value = 0.000),but the difference of expression of HBD-3in the three groups was found to be statistically insignificant.IIIConclusion: This study reported increased expression of HBD-3 in seraof patients with warts irrespective of their clinical type (plane, plantar orcommon).This finding may denote a systemic, not only a local, antiviralrole in host defense against warts .