Background: Heat shock protein (60 kd HSP) has been implicated in the etiology of Behçet's disease, but its expression at sites of inflammation is unknown. Objective: Our aim was to investigate local HSP 60 expression and to quantify T-cell receptor (TCR) γδ-positive cells, which are known to respond to HSP peptides. Methods: Patients with active Behçet's disease (n = 21) and controls (n = 18) were included. Flow cytometric analysis was performed on peripheral blood to investigate TCR γδ-positive cell counts. Biopsies were performed on active skin lesions, and immunohistochemical analysis was performed by a streptavidin-biotin method using the monoclonal ML-30 antibody; HSP staining intensity and distribution were evaluated in a blinded fashion. Immunhistochemical studies were performed to quantify TCR γδ-positive cells at lesional sites. Results: Mucocutaneous lesions of patients with Behçet's disease had statistically significantly increased expression of HSP 60/65. Peripheral blood TCR γδ-positive cell counts were similar in both groups. However, lesional skin of patients with Behçet's disease had significantly increased γδ-positive T-cell counts. Conclusion: Up-regulation of HSP expression was found at lesional skin sites in Behçet's disease. The increased number of TCR γδ-positive cells, which are known to respond to HSP peptides, may support the function of HSPs in the etiology of Behçet's disease. However, these findings may also be an epiphenomenon that needs to be further investigated. (J Am Acad Dermatol 2001;45:904-9.)