Six patients with generalized Wegener's granulomatosis are reported. All patients were treated with adrenocorticoids and a cytotoxic drug, either an alkylating agent or purine antagonist. Five patients are alive after a minimum of 15 months and a maximum of 96 months of observation. Disease activity was suppressed and renal function was maintained at a satisfactory level or improved during therapy in the survivors. In one patient a remission occurred after 84 months of therapy, with no recurrence of disease 12 months after the withdrawal of medications. One patient died when bone marrow depression developed after nitrogen mustard administration, with evidence of severe disseminated disease found at necropsy. The addition of cytotoxic drugs early in the course of even severe generalized Wegener's granulomatosis may help control the disease, reduce the requirement for adrenocorticoids, and significantly improve the prognosis of the illness.