Iodine-123 metaiodobenzylguanidine (123I-MIBG) radioaerosol is of potential use in the investigation of the neuroadrenergic function of the lungs; however, before the method can be successfully employed the following issues need to be clarified: (1) Does the nebulization affect the radiochemical purity of 123I-MIBG? (2) Is the pulmonary distribution of inhaled 123I-MIBG homogeneous in normal subjects? (3) Does the pulmonary clearance of inhaled 123I-MIBG reflect the functional status of the neuroadrenergic system of the lungs? In this study we performed: (1) a chromatographic study of nebulized 123I-MIBG; (2) a quantitative evaluation of the lung distribution of 123I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) and (3) an assessment of 123I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with 99mTc-DTPA. For these purposes, eight normal subjects were divided randomly into an "MIBG group" and a "DTPA group" (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized 123I-MIBG ranged between 97.18% and 98.70%. The lung distribution of 123I-MIBG, as judged by the aerosol penetration index, was identical to that of 99mTc-DTPA under all study conditions. The 123I-MIBG clearance rate was slower than that of 99mTc-DTPA under baseline conditions (135+/-32 min vs 69+/-27 min, P<0.01) and increased significantly after propranolol administrations, while the 99mTc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of 123I-MIBG; (2) the lung distribution of 123I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of 123I-MIBG reflects the functional status of the neuroadrenergic system of the lungs. Thus this scintigraphic method is suitable for research and perhaps for future clinical use.