Left ventricular rupture was studied in 849 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size. Although documented rupture occurred in only 14 cases (1.7%), it accounted for 14% of in-hospital mortality. Seven of the 14 ruptures occurred within 2 days and 10 within 4 days of the MB-creatine kinase-determined onset of infarction. Three easily determined baseline characteristics defined a set of patients with a markedly increased risk of myocardial rupture. Rupture was 9.2 times more likely to occur in patients with all of the following characteristics than in the remaining patients: (1) no history of previous angina or myocardial infarction, (2) ST segment elevation or signs of Q wave development on the initial ECG, and (3) peak MB-creatine kinase value (greater than or equal to 150 IU/L). The risk of myocardial rupture with these three characteristics was 5.5%. Although these predictors are likely to be of little therapeutic value for free wall rupture, since most patients with that complication die within minutes of its onset, they may aid in alerting physicians to the early diagnosis and timely surgical correction of ventricular septal rupture.