Twelve patients with the long QT syndrome were studied to determine the usefulness of 123I-metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPECT) at 2 h and 6 h after injection; the results were compared to 10 healthy volunteers (controls). Uptake of MIBG in the left ventricle at 2 h after injection was significantly reduced in patients with the long QT syndrome (1.43 +/- 0.13 vs 1.66 +/- 0.15 in controls, heart-to-mediastinum ratio, P < 0.002) and washout after 6 h was faster on a planar view image. Decreased MIBG uptake could be observed preferentially in the anterior and lateral walls near the apex. The half-time values of MIBG washout from the left ventricle were significantly reduced in the long QT syndrome (6.4 +/- 1.5 h) compared to controls (16.7 +/- 15.3 h, P < 0.002). In three cases, the same pattern of disturbed activity distribution was maintained even after surgical left cardiac sympathetic denervation. The present results strongly support the hypothesis that an inhomogenous regional distribution of sympathetic nerve terminals accompanied by an overall reduction in their absolute number may play an important role in the pathogenesis of the long QT syndrome. Additional functional disturbances, possibly related to the uptake of catecholamines in the left ventricle may coexist with regional inhomogeneity of nerve terminals. The differences observed from one case to the other may be related to the variation in severity of the disease. MIBG SPECT imaging seems an interesting new tool for the quantitative assessment of presynaptic sympathetic nerve terminal disturbances in the left ventricle of patients with the long QT syndrome.