Inferolateral early repolarization (ER) and Brugada syndrome manifest with J waves. Isoproterenol suppresses recurrent ventricular arrhythmias while reducing J waves in both disorders. To characterize the effect of isoproterenol on J waves. We analyzed the impact of isoproterenol on J waves in 20 patients with Brugada-type electrocardiogram (Br group) and 38 patients with ER (ER group). In the ER group, J waves were present in inferior leads in 32 patients (84%) and in lateral leads in 23 patients (61%). Isoproterenol increased the heart rate by 75 beats/min in the ER group and by 71 beats/min in the Br group (P = .20). The incidences of persistent (≤ 0.05-mV decrease), decreased, and normalized J waves (residual J wave ≤ 0.05 mV) were 20%, 80%, and 0% for Br group patients and 29%, 8%, and 63% for ER group patients, respectively (P <.001). Within the ER group, inferior J waves persisted in 34% of the cases, decreased in 9%, and normalized in 56% whereas lateral J waves always normalized (P <.001). Baseline QRS width was broader in ER group patients with persistent J waves (90 ms vs 80 ms; P = .003) and was unchanged with isoproterenol (90 ms; P = .19), whereas it decreased in the remaining patients (75 ms; P <.001). J-wave syndromes have distinct regional sensitivity to beta-adrenergic stimulation. J waves may persist in a subset of patients with right precordial and inferior J waves but never in lateral location. This heterogeneous response to isoproterenol may indicate distinctive mechanisms for Brugada and ER patterns, including depolarization abnormalities or ion channel sensitivity.