The conventional interpretation of ejection fraction change with exercise may be limited because it does not consider the rest value, define equivocal responses or integrate wall motion data reproducibly. Thus, a format was developed for combined interpretation of rest and exercise radionuclide ejection fraction and wall motion by reviewing the reported data for the exercise responses of patients without prior myocardial infarction. The ejection fraction data of 202 normal patients and of 259 patients with coronary artery disease were first fitted to beta distributions. The true positive and false positive rates for coronary disease for each combination of rest and exercise ejection fraction were then determined directly from these distributions. A given rest/exercise ejection fraction combination was "normal" if the false positive rate was greater than the true positive rate, or "abnormal" if the true positive rate was greater than the false positive rate, and "equivocal" when the rates were similar (within a 50% confidence interval). This analytic format, which predicted an inverse relation between rest ejection fraction and the change required with exercise, was then validated prospectively in 854 patients without myocardial infarction (557 with and 297 without angiographic coronary artery disease). Using the conventional criterion of an abnormal test result (less than 0.05 absolute rise in ejection fraction with exercise or a wall motion abnormality), sensitivity was 85 +/- 2% and specificity only 42 +/- 3%. The statistical format had a sensitivity of 70 +/- 2% and specificity of 70 +/- 3%, resulting in a twofold increase in information content. This format has at least two advantages over conventional interpretation: 1) it provides an explicit definition of equivocal responses; and 2) it reproducibly integrates discordant ejection fraction and wall motion responses and allows for the combined analysis of other nonscintigraphic observations, such as age and sex.