BACKGROUND: Behçet's syndrome is a chronic systemic immuno-inflammatory disorder affecting multiple organs with generalized vasculitis of arteries and veins. Although the aetiology is still unknown, endothelial dysfunction is one of the most prominent features in Behçet's syndrome. The skin pathergy reaction (SPR) is a non-specific hyperreactive lesion formation that is one of the major features and diagnostic criteria of the disease. It develops after 24-48 h at the site of the needle-prick, especially in the exacerbation period, and it is very similar to the erythematous papules or pustules that appear spontaneously in patients with Behçet's syndrome. Therefore, an investigation into the formation of the SPR lesion may contribute to the pathophysiology of skin lesions of this unique disorder. OBJECTIVE: To evaluate the immunological features of SPR formation by assessing the immunohistochemical staining of cell adhesion molecules and endothelial growth factor markers such as E-selectin, P-selectin and endoglin (CD 105). METHODS: Patients with Behçet's syndrome showing positive (n = 15) or negative (n = 10) SPR and 15 age- and sex-matched hospital-based healthy control subjects from a similar ethnic background were included in this study. Patients were divided into active and inactive stage by clinical findings and acute-phase reactant parameters including erythrocyte sedimentation rate (ESR) and neutrophil count. Punch biopsy specimens were obtained both from the lesion site on the forearms at 48 h and from normal skin approximately 5 cm adjacent to the SPR site. A biopsy was also obtained from the test application site in Behçet's syndrome patients with negative SPR and healthy volunteers. Biopsy specimens were then evaluated by immunohistochemical staining. RESULTS: Immunohistochemical examination demonstrated a mixed inflammatory cell infiltrate around the vessels and skin appendages that extended somewhat into the deep dermis. A positive segmental staining of E-selectin and P-selectin was noted in the endothelial cells of biopsies obtained from the patients with positive SPR. A positive segmental staining of CD 105 in the endothelial cells was also observed in the same group of patients. However, the immunostaining of the same markers was found to be negative in the biopsies obtained from normal skin of SPR-positive patients, SPR-negative patients and healthy control subjects. Both acute-phase reactant levels were significantly higher in the active stage than in inactive patients or healthy controls. CONCLUSION: Interaction of cellular adhesion molecules together with endothelial proliferation may play an important role in the formation of SPR lesions in patients with Behçet's syndrome. The involvement of the vascular endothelium in a large number of diseases including Behçet's syndrome supports the importance of vascular-specific adhesion molecules for their aetiopathogenesis.