Bullous pemphigoid (BP) usually responds well to conventional therapies, although some severe cases show less response to various therapies or develop side‐effects due to long‐term drug administration using high doses. Most BP patients are elderly and are thus prone to systemic deterioration or unfavorable outcome. In the present study, we investigated the efficacy of interferon‐γ on severe BP patients resistant to conventional therapies. Interferon‐γ was administered to 10 severe BP patients at a dose of 2 million Japan reference units (JRU) once a day for 7 consecutive days by i.v. infusion in addition to oral corticosteroids. The degree of improvement in the clinical symptoms, serum interleukin (IL)‐4, IL‐5, and plasma RANTES concentrations, as well as the results of indirect immunofluorescence and BP180 enzyme‐linked immunosorbent assay index values, were compared before and after the 7‐day drug administration. Among the nine patients whose clinical symptoms were evaluated, an improvement was observed in all patients. Except for one patient, the serum IL‐4 concentrations decreased and similar results were observed for the serum IL‐5 concentration. All five patients in whom the plasma RANTES concentration was measured showed decreased levels. The indirect immunofluorescence titers decreased in only four patients. However, in seven patients in whom index values of BP180 enzyme‐linked immunosorbent assay were evaluated, all patients showed significant decrease of the index values. These results suggest that, in severe BP patients refractory to conventional therapies, interferon‐γ in addition to oral corticosteroids is effective and thus should be considered for further clinical use.