This article introduces a novel concept of abnormal intra-QRS potentials (AIQPs) associated with myocardial ischemia. AIQPs are microvolt-level potentials--subtle alterations in the QRS of the high-resolution electrocardiogram (ECG)--isolated from the unfiltered signal-averaged ECG (SAECG) by a method of mathematical modeling. The aims of the study were (1) to determine the characteristics of potentials in the SAECG related to ischemically altered activation during percutaneous transluminal coronary angiography (PTCA), (2) to determine their relationship with standard 12-lead ECG variables, and (3) to investigate whether AIQPs have a specific pathophysiologic basis in myocardial ischemia. Continuous high-resolution ECG data were acquired from 12 patients before, during, and after PTCA. SAECGs were computed every 60 seconds using an enhanced method of signal averaging. AIQP, ST-segment deviation, and changes in standard ECG QRS duration were measured in each 1-minute SAECG. AIQP amplitudes increased significantly during balloon inflation, compared with the preinflation state. AIQPs exhibited a greater prevalence (12 of 12 patients) than ST-segment deviation changes of more than 100 microV (7 of 12 patients), or measurable changes in standard QRS duration (4 of 12 patients). In patients with significant changes in 12-lead ECG variables during balloon inflation, AIQPs were strongly correlated with both ST-segment and QRS-duration changes. AIQP timing was correlated with the artery occluded, suggesting a specific, ischemia-influenced origin of the signal. AIQPs show promise as a time-localized, sensitive new ECG marker of ischemically altered ventricular activation.