The diagnosis and treatment of pheochromocytoma depend critically on effective means to localize the tumor. Computed tomography and magnetic resonance imaging have good sensitivity but poor specificity for detecting pheochromocytoma, and nuclear imaging approaches such as (131)I-metaiodobenzylguanidine scintigraphy have limited sensitivity. Here we report initial results using 6-[(18)F]fluorodopamine positron emission tomography (PET) scanning in the diagnostic localization of pheochromocytoma. Twenty-eight patients with known or clinically suspected pheochromocytoma underwent PET scanning after intravenous injection of 6-[(18)F]fluorodopamine. Of the 28 patients, 9 had surgical confirmation of the tumor, 8 had previously diagnosed metastatic pheochromocytoma, and 11 had plasma levels of metanephrines that were within normal limits. All 9 patients with surgically proven pheochromocytoma had abnormal 6-[(18)F]fluorodopamine PET scans that identified the tumors. All 8 patients with metastatic pheochromocytoma had extra-adrenal sites of 6-[(18)F]fluorodopamine-derived activity. Of the 11 patients with normal plasma levels of metanephrines, 9 had negative 6-[(18)F]fluorodopamine PET scans, 1 had extra-adrenal foci of 6-[(18)F]fluorodopamine-derived activity, and 1 had symmetric uptake of 6-[(18)F]fluorodopamine in the region of the adrenal glands. In patients with known disease, 6-[(18)F]fluorodopamine PET scanning can detect and localize pheochromocytomas with high sensitivity. In patients in whom the diagnosis of pheochromocytoma is considered but excluded because of negative plasma metanephrine results, 6-[(18)F]fluorodopamine PET scans are consistently negative. These findings justify a clinical trial of 6-[(18)F]fluorodopamine PET scanning as a diagnostic tool.