Excess sympathetic nervous activity was proposed to play a crucial role in the pathogenesis of transient left-ventricular apical ballooning (TLVAB, also known as Tako-Tsubo cardiomyopathy). This study was conducted to assess presynaptic adrenergic alterations in the dysfunctional myocardium of patients with TLVAB. Ten consecutive patients undergoing coronary angiography for acute coronary syndrome who fulfilled the proposed Mayo Clinic criteria for the diagnosis of TLVAB were investigated. Myocardial iodine-123 metaiodobenzylguanidine ((123)I-MIBG) studies (planar and single-photon emission computed tomography [SPECT]) were performed to evaluate adrenergic innervation. Concomitantly, myocardial perfusion was assessed by means of technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT. In all patients, angiography revealed typical ballooning of the left-ventricular (LV) apex and hyperkinesis of the basal LV segments (overall ejection fraction, 41% +/- 5% [mean +/- SEM]). Planar (123)I-MIBG scans revealed decreased heart-to-mediastinum ratios at early (20 minutes) and delayed (4 hours) images (2.1 +/- 0.1 and 1.9 +/- 0.1, respectively). The cardiac washout rate of (123)I-MIBG on the late images was increased to 34% +/- 3%. The (123)I-MIBG uptake on SPECT scans was obviously reduced in the akinetic LV apex (defect score, 3.30 +/- 0.34), whereas (99m)Tc-MIBI SPECT indicated normal or only mildly reduced perfusion within this region (defect score, 0.89 +/- 0.35). Our study indicates a functional alteration in presynaptic sympathetic neurotransmission in patients with TLVAB, and suggests a pathophysiologic explanation of the impairment of LV function.