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Repolarization alternans (RPA) is prognostic of sudden cardiac death and is thought to be mechanistically linked to the initiation of ventricular tachyarrhythmias. Thus, implantable cardiac device detection of RPA may be therapeutically valuable. Because alternans detection is currently limited to surface electrocardiograms, we investigated whether RPA could be measured using a single right-ventricular endocardial lead in humans. Such a location was chosen because it is consistent with the requirements for long-term implantable-device implementation. During diagnostic electrophysiological testing, 28 patients (23 male, 5 female; 61±15 years) were evaluated for surface T-wave alternans (TWA; the current "gold standard" for RPA detection) and endocardial RPA during 5 min of 550-ms right-atrial pacing. Power spectral analysis indicated that 11/28 patients had both surface TWA and endocardial RPA, 9/28 patients had neither, and 8/28 patients had discordant results (71% concordance; p=0.02). Importantly, unlike surface TWA, endocardial RPA was detectable on a beat-to-beat basis. Given the putative mechanistic link between RPA and ventricular arrhythmias, beat-to-beat endocardial RPA detection might be of diagnostic or therapeutic utility.