Lymphoid cells from 4 of 5 patients diagnosed as pemphigus vulgaris (PV) and 6 of 7 patients diagnosed as bullous pemphigoid (BP) demonstrated specific cell-mediated immunity by the production of migration inhibitory factor (MIF) in the presence of autologous epidermal saline extracts. Clinical treatment of these patients with immunosuppressive agents resulted in a state of unresponsiveness of their lymphoid cells to similar concentrations of the antigen. Controls consisted of lymphoid cells from patients with bullous burns or various drug allergies which failed to show significant MIF production in the presence of autologous skin extract. These studies suggest that both PV and BP patients posses cell-mediated immunity (CMI) to their own autologous tissue antigens and this CMI may play a role in the pathogenesis of these diseases.