BACKGROUND The importance of eosinophils in the pathogenesis of the major forms of pemphigoid (bullous pemphigoid, cicatricial pemphigoid, herpes gestationis) remains to be confirmed. METHODS To evaluate the role of eosinophilic infiltrates in these diseases and to detect the presence and activity of eosinophils, we compared the serum levels of eosinophil cationic protein (ECP), an eosinophil-derived protein, in 11 healthy subjects and in 10 patients with pemphigoid diseases (8 with bullous pemphigoid, one with cicatricial pemphigoid, and one with herpes gestationis). The serum of two patients with epidermolysis bullosa acquisita (EBA) and one with linear IgA bullous dermatosis (LABD) were utilized as a further control. RESULTS There was a significant difference between the mean of serum ECP levels in patients with pemphigoid diseases (25.1 +/- 12.3 micrograms/L, M = SD) and control subjects (2.30 +/- 2.41, micrograms/L +/- SD 2.41) (T = 4.272 P < 0.0001). The two patients with EBA (10.8 and 17.7 micrograms/L) showed contrasting results; the patient with LABD had normal ECP serum levels. The serum levels of ECP were not significantly correlated with the blood eosinophil count (R = 0.103; P = 0.777) in any of the cases. CONCLUSIONS In pemphigoid disease, the serum levels of ECP seem to be correlated with the activated secreting and tissue-damaging eosinophils found in the dermis, supporting the concept of an active participation of eosinophils in generating cutaneous lesions.