New Findings What is the central question of this study? High titres of autoantibodies against the second extracellular loop of the (1)-adrenergic receptor ((1)-AAs) can be detected in the sera of patients with ventricular arrhythmias, but a causal relationship between (1)-AAs and ventricular arrhythmias has not been established. What is the main finding and its importance? Monoclonal (1)-AAs ((1)-AR mAbs) were used in the experiments. We showed that (1)-AR mAbs increased susceptibility to ventricular arrhythmias and induced repolarization abnormalities. Antibody adsorption of (1)-AAs will be a potential new therapeutic strategy for ventricular arrhythmias in patients with high titres of (1)-AAs. High titres of autoantibodies against the second extracellular loop of the (1)-adrenergic receptor ((1)-AAs) can be detected in sera from patients with ventricular arrhythmias, but a causal relationship between (1)-AAs and ventricular arrhythmias has not been established. In this work, ECGs of guinea-pigs and isolated guinea-pig hearts were recorded. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were evoked by programmed electrical stimulation of the left ventricular epicardium of isolated guinea-pig hearts. The monophasic action potential and effective refractory period of the left ventricle were recorded in paced isolated guinea-pig hearts. Furthermore, to increase the specificity, monoclonal autoantibodies against the second extracellular loop of the (1)-adrenergic receptor ((1)-AR mAbs) were used in all experiments. The results showed that (1)-AR mAbs induced premature ventricular contractions in guinea-pigs and isolated guinea-pig hearts. In addition, (1)-AR mAbs decreased the threshold of VT/VF and prolonged the duration of VT/VF. Furthermore, (1)-AR mAbs shortened the corrected QT interval and effective refractory period, and prolonged late-phase repolarization of the monophasic action potential (MAPD(90-30)). These changes in electrophysiological parameters might be attributed, at least in part, to the arrhythmogenicity of (1)-AR mAbs.