Increases in electrocardiographic R-wave amplitude in humans have been described with positive and negative dynamic exercise test findings, episodes of variant angina and myocardial ischemia and infarction. The role of factors other than acute reversible ischemia in the genesis of these R-wave size alterations is unclear. To evaluate the contribution of acute ischemia to changes in R-wave size in the absence of other confounding variables, electrocardiograms were recorded before and during coronary angioplasty balloon inflation. The frontal leads and V1, V2, V5 and V6 were recorded during the last 10 seconds of coronary occlusion in 20 patients and intracoronary epicardial electrograms were recorded continuously during balloon inflation in 10 patients. Inflations were 8 +/- 2 atm for 52 +/- 36 seconds. Chest pain occurred in 26 of 30 patients with balloon inflation and ST elevation occurred in 22. No significant increases in R amplitude were noted in any lead or in the sum of the R waves in all leads, including intracoronary electrograms. In contrast, R amplitude tended to decrease. The initial decrease in both surface and epicardial R amplitude was similar to the first of the biphasic changes observed in animal models. An increase in R-wave amplitude is not by itself always a marker for myocardial ischemia, but depends on severity and duration of the process.