Bullous pemphigoid (BP) is an auto-immune blistering skin disease associated with the presence of autoantibodies directed to BP antigens located at the basement membrane zone of the dermal-epidermal junction. The present study was designed to test for the involvement of cellular immune mechanisms in the pathogenesis of blister formation. An immunohistochemical analysis of the lesional, peri-lesional, and pre-lesional mononuclear cell infiltrates, performed in 7 BP patients, revealed the following observations: 1) all the skin biopsies contained a high percentage of mononuclear cells within the inflammatory cellular infiltrate; 2) T cells (CD3+, CD45RO+), with a phenotype of activated helper T cell (CD4+, CD25+) were consistently found; 3) T cells were found beneath the bullae but, more importantly, also at the dermal-epidermal junction in close contact with the basement membrane zone in pre- and peri-bullous lesions. These results show that activated T cells are found at the early phase of the onset of BP lesions and suggest that they could play a role, in association with autoantibodies, in the pathogenesis of bulla formation.