Background Early repolarization (ER) in the inferior electrocardiogram leads is associated with idiopathic ventricular fibrillation, but the majority of subjects with ER have a benign prognosis. At present, there are no risk stratifiers for asymptomatic ER. Objective To examine the response to ajmaline provocation and exercise in potentially high-risk subjects with ER and without a definitive cardiac diagnosis. Methods Electrocardiographic data were reviewed for ER at baseline and during ajmaline and exercise testing in 229 potentially high-risk patients (mean age 37.7±14.9 years; 55.9% men). ER was defined as J-point elevation in≥2 consecutive leads and stratified by type, territory, J-point height, and ST-segment morphology. Results Baseline ER was present in 26 (11.4%; 19 men) patients. During ajmaline provocation and exercise, there were no new ER changes. ER with rapidly ascending ST-segment and lateral ER consistently diminished. There were 7 patients with persistent ER during ajmaline and/or exercise. They were all men with inferior or inferolateral ER and horizontal/descending ST segment. Those with persistent ER during exercise were more likely to have a history of unexplained syncope than those in whom ER changes diminished (P<.01). Subtle nondiagnostic structural abnormalities were demonstrated in 3 of these patients. Conclusions ER with horizontal/descending ST-segment morphology in the inferior or inferolateral leads that persists during exercise is more common in patients with prior unexplained syncope and may identify patients at higher risk of arrhythmic events. ER that persists during ajmaline provocation and/or exercise may reflect underlying subtle structural abnormalities and should prompt further investigation.