This article summarizes the management of 22 cases of pyoderma gangrenosum over the past four years at the hospital of the University of Pennsylvania, Philadelphia. Eighteen patients with pyoderma gangrenosum were studied using the most sensitive routine laboratory method for detection of monoclonal immunoglobulins, immunofixation electrophoresis. Four cases of IgA gammopathy were detected, confirming previous reports of the incidence of monoclonal gammopathy in pyoderma gangrenosum. High-dose glucocorticoid therapy (pulse therapy) is an effective treatment for some severe, refractory cases of pyoderma gangrenosum. Eight patients were treated with pulse therapy. Six responded favorably, and none had serious complications.