The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg) every 3 months. Seven of these patients had bone and soft tissue metastases, 4 had only soft metastases, and 4 had only bone metastases. The follow-up period ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4 mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative activity from 11.1-85.90 GBq (300-2322 mCi). The absorbed cumulative dose in tumors ranged from 12-155 Gy. A beneficial effect of the treatment was observed in 9 patients (60%). No complete remission of the disease was observed. Seven patients died during the study, among whom 4 never responded to the treatment. Seven had hormonal responses (4 complete and 3 partial), with a duration ranging from 5-48 months. Among these patients, 4 relapsed, and 3 died within 3 months. Five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29-54 months. All patients with a hormonal response had objective improvement in clinical status and blood pressure. There was no clear-cut relationship between the cumulative dose and the responses. The main side-effect observed in 1 patient with widespread bone metastases after three doses (12.9 GBq) was a pancytopenia, which resolved after treatment was discontinued. This study suggests that repeated [131I]MIBG treatment could be effective in patients with advanced malignant pheochromocytoma.