The immunoreactive leukotriene B4 (i-LTB4) and i-LTC4 content in the blister fluids of patients with bullous pemphigoid (BP) was determined by radioimmunoassay. Their amounts significantly exceeded those noted in superficial dermal burn patients and those in the fluids of suction blisters produced on normal human skin. When either BP blister fluids or BP-IgG from the patient sera were injected into guinea pig skin, neutrophil and eosinophil infiltrates were produced in the dermis. In addition, the dermis was noted to undergo marked edematous change. A single oral administration of a selective inhibitor of 5-lipoxygenase 1 hr before the intracutaneous injection of BP-IgG was found to significantly inhibit cell infiltrates. Furthermore, the inhibitor partly suppressed dermal epidermal separation. On the basis of these results. LTB4 and LTC4 appear to be generated in the skin lesions of BP, the former attracting granulocytes to the dermis and the latter, causing exudation.