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To test the hypothesis that patients at risk of future cardiac events can be identified by sub-maximal exercise testing with radionuclide ventriculography (RVG), 61 patients were studied a mean of 19 +/- 1.0 days (+/- SEM) after acute myocardial infarction (MI). RVGs were used to measure left ventricular ejection fraction (LVEF), wall motion score (WMS), end-diastolic volume (EDV) and end-systolic volume (ESV), and the ratio of systolic blood pressure to ESV (P/V index) at rest and during submaximal exercise. Frank lead ECGs were analyzed for ST-segment change and arrhythmias. These patients were followed for a mean of 9.6 months (60 for 6 months or more and one for 3 months) to determine the incidence of cardiac death, recurrent MI, unstable or medically refractory angina, persistent congestive heart failure (CHF) or limiting angina; these problems were considered to be important cardiac events. At the 6-month follow-up, 37 patients had important complications: four patients died, five had MI, seven had unstable or medically refractory angina, 11 had persistent CHF and 10 had severe limiting angina. The sensitivity and specificity of RVG in predicting the important postinfarct complications listed above were 95% and 96% for failure to increase LVEF by at least 5 units, 95% and 96% for an increase in ESV of more than 5%, 97% and 88% for failure of the P/V index to increase by more than 35%, and 81% and 88%, respectively, for a decrease in WMS. The sensitivity and specificity of the ECG in predicting important complications were 54% and 58%, respectively. The rest and submaximal exercise RVG variables, the ECG, a history of MI, the location of the infarction, Killip class III, age, sex, and maximal work load performed were analyzed statistically to determine the best predictors of prognosis. The change with exercise in LVEF, ESV and the P/V index were most significant variables in predicting prognosis during the 6-month follow-up period. When patients with subsequent cardiac events were separated into those with death, recurrent MI and unstable or medically refractory angina as major cardiac events, and patients with persistent CHF and limiting angina as less important ("minor") cardiac events, only the peak submaximal exercise LVEF and history of MI were significant in distinguishing these groups. In patients without important cardiac events during the 3- and 6-month follow-up, 70% and 88%, respectively, no abnormality in the responses of LVEF, ESV, or P/V index to submaximal exercise. These results suggest that submaximal exercise testing with RVG is a highly sensitive means of classifying patients at the time of hospital discharge after MI according to the likelihood of having cardiac events during the ensuing 6 months.