A 61-year-old man suffering from active generalized scleroderma developed pemphigus foliaceus after 9 months of D-penicillamine therapy, 900-1200 mg daily. At the same time, he developed proteinuria. Upon discontinuation of the drug, the proteinuria quickly resolved, but the bullous disease was still active one year later, with development of fresh blisters and intercellular deposits of immunoglobulin G and complement C3. The theory is proposed that D-penicillamine alters the epidermal cement substance, rendering it antigenic and thus initiating a vicious circle.