Thirty-eight patients (24 men and 14 women) with an acquired ventricular sepatal defect during acute myocardial infarction (AMI) (rupture group) were studied and their clinical and necropsy findings were compared with 50 patients who died during their first AMI without rupture (nonrupture group). The frequency of systemic hypertension (54 vs 52%), angina pectoris (28 vs 22%) and congestive heart failure (5 vs 0%) before the fatal AMI was similar for both rupture and nonrupture groups. Mean heart weights for men (498 vs 526 g) and women (397 and 432 g) with and without septal rupture also were insignificantly different. Whereas previous studies of fatal AMI cases have shown that 50% of cases of fatal AMI without rupture have left ventricular scars, only 4 (10%) of the rupture cases had a left ventricular scar before the infarct that ruptured. The rupture group had a significantly more frequent (p < 0.01) posterior location of the infarcts (74 vs 40%) and, therefore, a higher frequency of associated right venticular infarcts (50 vs 18%). The number of 3 major (right, left anterior descending and left circumflex) epicardial coronary areries narrowed at some point > 75% in cross-sectional area of atherosclerotic plaque was the same in both groups. The percent of these 3 arteries totally occluded or nearly so (> 95% in cross-sectional area) by plaque was significantly less (p < 0.001) in the rupture group compared with the nonrupture group (9 of 99 arteries [9%] vs 38 of 144 arteries [26%]). Analysis of each 5-mm long segment of these arteries in each group disclosed that the rupture group had significantly less narrowing than the nonrupture group. Of the 825 five-mm segments of artery examined in the rupture group (18 patients), only 101 (13%) were narrowed > 75% in cross-sectional area by plaque; in contrast, of the 1,848 five-mm segments in the nonrupture group (38 patients), 508 (28%) were narrowed to this degree by plaque (p < 0.01). Thus, rupture of the ventricular septum primarily is a complication of the first AMI. It is associated with less severe coronary arterial narrowing than observed in fatal AMI without rupture, and it is a more frequent complication of posterior (inferior) than anterior wall AMI.