In cryostat sections from lesional skin of a patient with pemphigus, a typical pattern of IgG deposits was detected at the epidermal intercellular space. However, there were no deposits of complement (C) components. By the highly sensitive APAAP technique using monoclonal antibodies, it was demonstrated that the IgG deposits consisted exclusively of IgG4. IgG subclass analysis of serum autoantibodies against epidermal intercellular substance antigen revealed an identical subclass restriction to IgG4. The IgG4 portion of the serum IgG fraction was significantly increased. Since IgG4 is known to be a an almost ineffective activator of complement, the lack of deposits of C components is not surprising. Our ex vivo observations suggest that complement is not essential for the induction of pemphigus acantholysis.