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Erythema dyschromicum perstans (EDP) is a pigmentary disease of unknown etiology in which damage to basal cells is thought to be mediated by adhesion molecules. The aim of this study was to characterize the histopathology and immunopathology of EDP. Forty-three patients from Medellín, Colombia, with the diagnosis of EDP were evaluated. Skin biopsy specimens were obtained for histopathology and immunohistochemistry, using monoclonal antibodies directed against the following markers: CD4, CD8, CD56, CD1a, CD68, CLA, HLA–DR, ICAM-1 and LFA-1α.A dermal lymphocytic infiltrate was observed in all cases, with a perivascular location in 86%. Other histologic features included melanophages in all specimens, vacuolization of the basement membrane zone (BMZ) 58% and exocytosis of lymphocytes (53.5%). The mean number of total leukocytes was 1510 cells mm−2 of tissue. There was a predominance of CD8+ T lymphocytes in the dermis and HLA–DR+, ICAM-1+ keratinocytes in the epidermis. Exocytosis of cutaneous lymphocyte antigen (CLA) + cells was observed in areas of BMZ damage, suggesting that response to antigenic stimulation may play a role in the development of EDP.