E-cadherin is a major homophilic cell-cell adhesion molecule of the skin. There are two forms of E-cadherin--membrane and soluble types. Although various abnormalities of the former type have been identified in some cutaneous diseases, information relating to the latter is sparse. We measured the concentrations of soluble E-cadherin in several cutaneous diseases, and found higher levels in sera from patients with bullous pemphigoid, pemphigus vulgaris, psoriasis vulgaris and inflammatory skin diseases, compared with controls. In psoriasis vulgaris the levels of soluble E-cadherin in sera correlated with the PASI score. In normal individuals, levels in suction blister fluid were double those in sera. These findings suggest that changes occur in circulating levels of soluble E-cadherin in skin disease, possibly reflecting increased turnover and/or proteolysis of cell-surface molecules in the epidermis.