5 of 6 adults with generalized granuloma annulare responded favorably to therapy with low-dose chlorambucil. 5 of the patients had lesions that were recurrent and long-standing and that resisted conventional modalities of therapy. Low-dose chlorambucil may be effective in a short-term therapy program but should be used only in patients with persistent, widespread, or unusual forms of generalized granuloma annulare. The program requires close patient and hematologic supervision.