Familial Mediterranean fever (FMF) is characterized by recurrent inflammation of serosal and synovial membranes. Despite the fact that it is a genetic disease, environmental factors, including infections, are shown to be triggering factors associated with the precipitation of attacks in FMF. Antimicrobial peptides (AMPs) are components of innate immunity which exert antimicrobial activity against many microorganisms. Human AMPs; cathelicidin (LL37) and defensins have immunomodulatory properties and are involved in the pathogenesis of many inflammatory disorders. Hence, we investigated serum AMPs in 23 newly diagnosed FMF patients. Blood samples were obtained at baseline, 6 months after initiation of colchicine and during an attack. Twenty-four healthy individuals constituted the control group. The concentrations of LL37, alpha-1, beta-1 and beta-2 defensins were determined by ELISA. Serum AMPs did not change during attacks and did not correlate with acute phase reactants. However, serum LL37 and defensins were found to be remarkably higher in FMF patients compared to healthy individuals both at baseline and 6 months after initiation of colchicine therapy which suggest that AMPs might have a role in the pathogenesis of FMF.