The role of lymphocytes in the pathogenesis of bullous pemphigoid was examined by assaying the blister fluid obtained from bullous pemphigoid patients for the presence of the lymphokine, lymphotoxin. Blister fluids from six bullous pemphigoid were assayed on L-929 target cells for the presence of cytolytic molecules in the standard lymphotoxin assay. Three of six blister fluids obtained from bullous pemphigoid patients and one linear IgA bullous dermatosis patient contained significant levels of cytolytic activity. Control blister fluids from suction blisters, herpes, pemphigus, and toxic epidermal necrolysis patients did not contain cytolytic activity. Serum from five bullous pemphigoid patients also had no cytolytic activity. Neutralization studies using rabbit anti-alpha-lymphotoxin demonstrated that 54 to 88% of the cytolytic activity found in bullous pemphigoid blister fluid was due to alpha-lymphotoxin. These results indicate that lymphotoxin is locally released in the skin of bullous pemphigoid lesions and is detectable in blister fluids.