We have encountered two healthy volunteers with significant reductions of myocardial [123I]MIBG (metaiodobenzylguanidine) uptake and rapid clearance. In one of these subjects (a 31-yr-old man), we performed additional examinations to clarify the mechanism of the abnormal myocardial MIBG uptake. There was no abnormality on orthostatic test, maximal exercise test (bicycle ergometer) or in plasma norepinephrine concentration. Nevertheless, power spectral analysis (PSA) of heart rate variability revealed that the percent low frequency component (%LF), an index of sympathetic nerve activity, was increased. Furthermore, [123I]MIBG scintigraphy after oral administration of an alpha 2 agonist (guanabenz acetate; 4 mg) demonstrated that myocardial uptake and clearance of MIBG returned to normal, as did the %LF. These results suggest that reduced uptake and rapid clearance of myocardial MIBG in this subject was strongly related to the increased release of norepinephrine from sympathetic nerve terminals due to augmented sympathetic activity. This subject illustrated that unsuspected, subclinical variants of normal or abnormal sympathetic functions may pose a diagnostic pitfall in interpretating myocardial MIBG images.