This study examined the hypothesis that the polymorphism of Duffy antigen receptor for chemokines (DARC) predisposes to and/or influences the clinical manifestations of Behçet's disease. The serum levels of IL-8 and monocyte chemotactic peptide (MCP)-1, two DARC-binding chemokines, were investigated and related to this polymorphism. Twenty-eight patients with Behçet's disease and 30 healthy blood donors were included in the study. No null phenotypes were found among the patients studied, and the frequencies of the other phenotypes (Fy((a+b-)), Fy((a+b+)), and Fy((a-b+))) did not significantly differ from those found in the blood donor group or reported in the general Caucasian population. No difference was found between the single phenotypes in terms of IL-8 and MCP-1 serum levels, and no relevant association between the clinical characteristics, Behçet's disease-associated human leukocyte antigen (HLA)-B51, and single phenotypes was observed. This investigation indicates that DARC is not a genetic trait significantly associated with or predisposing to Behçet's disease, at least in Caucasian Italians. However, the role of this polymorphism in the development and in the clinical course of the disease awaits further investigation.