Apart from relieving effects of secreted catecholamines, treatments of malignant pheochromocytoma have achieved little success. When the radiopharmaceutical, meta-[131I] iodobenzylguanidine (I-131 MIBG ), was found to concentrate in some malignant pheochromocytomas, we calculated that this agent could impart therapeutic doses of radiation to these tumors. We therefore treated five patients with two to four doses of I-131 MIBG prepared in high specific activity, 8-11 Ci/mmol. Individual doses were given at 3- to 10-mo intervals and in 97- to 197-mCi amounts. Two patients exhibited subjective and objective benefits. Their tumors declined in size (to 28% and 30% of original volumes) and in hormone secretion (to 50% or less of baseline rates). The other three patients manifested few symptoms before treatment and showed few or no objective improvement afterward. The tumors of the patients who responded to I-131 MIBG (a) appeared to be more rapidly growing, (b) received more cumulative rads, and (c) were more predominantly in soft tissues (in contrast to bone) than those in the patients who obtained little benefit. No toxic effects were encountered during the treatments, and only minor and temporary untoward responses were seen later.