Hailey-Hailey disease (chronic benign familial pemphigus) is a chronic, recurrent blistering disorder characterized clinically by erosions occurring primarily in intertriginous regions and histologically by suprabasilar acantholysis. We report a case of Hailey-Hailey disease initially unresponsive to multiple topical corticosteroids, tetracycline, dapsone, ciclosporin, isotretinoin, prednisone, methotrexate, topical ciclopirox, tazarotene cream, pimecrolimus cream and tacrolimus ointment. Partial response of this patient's perineal disease was achieved with Amevive 15 mg weekly for 12 weeks, intramuscularly. To our knowledge, this case represents the first such published report of successful treatment of Hailey-Hailey disease using alefacept.