The purpose of the study was to assess the diagnostic utility of 6-[(18)F]-fluorodopamine ([(18)F]-DA) positron emission tomography scanning (PET) vs. [(131)I]-metaiodobenzylguanidine (MIBG) scintigraphy in patients with metastatic pheochromocytoma (PHEO). We studied 10 men and six women (mean age 38.2 +/- 11.5 yr) referred to our institution for metastatic PHEO; two patients were studied twice within a 2-yr interval. Imaging modalities included computed tomography (CT), magnetic resonance imaging (MRI), [(131)I]-MIBG scintigraphy, and [(18)F]-DA PET. Fifteen of 16 patients had positive findings on CT and/or MRI consistent with the presence of pheochromocytoma. [(18)F]-DA PET was positive in all patients, but seven patients had negative [(131)I]-MIBG scans. Thirty-eight foci of uptake were shown by both [(18)F]-DA PET and [(131)I]-MIBG scintigraphy, 90 only by [(18)F]-DA PET, and 10 only by [(131)I]-MIBG; most lesions were also visible on CT/MRI. In this initial series of patients with metastatic pheochromocytoma, [(18)F]-DA PET localized PHEO in all patients and showed a large number of foci that were not imaged with [(131)I]-MIBG scintigraphy. Thus, [(18)F]-DA PET was found to be a superior imaging method in patients with metastatic PHEO, in which correct detection of disease extension often determines the most appropriate therapeutic plan and future follow-up.