Pyoderma gangrenosum is a chronic ulceronecrotic inflammatory cutaneous disorder that can be associated with diseases such as rheumatoid arthritis (RA). No definitive treatment exists for this condition; steroids have been the mainstay of therapy, and the addition of immunosuppressives has been advocated. We describe 2 patients with pyoderma gangrenosum occurring in the setting of RA who, in addition to steroids, received pulse intravenous cyclophosphamide and had a remarkably good and lasting response. This is the first report of such a therapeutic approach. The pertinent literature is discussed. We conclude that pulse cyclophosphamide is another possible therapy for pyoderma gangrenosum.