Background: Prednisone alone or in combination with an immunosuppressive drug is usually effective in controlling bullous pemphigoid. However, corticosteroids often cause potentially hazardous side effects, especially in elderly patients. Objective: Our purpose was to evaluate low-dose treatment with methotrexate in elderly patients with generalized bullous pemphigoid. Methods: Oral methotrexate, at an initial dosage of 5 mg/wk, was given to 11 consecutive patients older than 70 years of age who were not responding to potent topical steroids. If the response was insufficient, the methotrexate dose was increased by 2.5 mg/wk to a maximum of 12.5 mg/wk. Results: All patients responded with a marked and rapid decrease in disease activity. The disease was controlled in the majority of patients (8 of 11) with 5 to 7.5 mg of methotrexate per week. Three patients required a weekly dose of 10 to 12.5 mg. At 24 months of follow-up 7 patients were in complete remission and did not require methotrexate. Conclusion: Our study suggests that low-dose oral pulse methotrexate constitutes an effective therapeutic alternative in elderly patients with generalized bullous pemphigoid.(J Am Acad Dermatol 1999;40:741-9.)