The development of a ventricular septal defect (VSD) following myocardial infarction is an uncommon complication which clinically can be confused with mitral insufficiency due to infarction of a papillary muscle. The clinical and hemodynamic records of six patients with documented acute VSD secondary to myocardial infarction were analyzed to determine which descriptors would be of value in clinically separating these two entities. All six of our patients had a right heart catheterization showing an oxygen step-up consistent with a VSD, and five had a large pulmonary wedge V wave suggesting concomitant mitral insufficiency. The echocardiogram showed only nonspecific chamber enlargement. Since these patients were being considered for open heart surgery to close the VSD, left and right cardiac catheterization including selective coronary arteriography was done. Despite large V waves being present in the pulmonary wedge and/or left atrial pressure tracing in five of the six patients, no mitral insufficiency was present on the left ventricular cineangiograms. It is concluded that a large pulmonary wedge and/or left atrial V wave does not necessarily indicate mitral insufficiency. Since both a VSD and mitral insufficiency are surgically correctable, patients who develop new holosystolic murmurs following myocardial infarction should have complete right and left heart catheterizations with LV angiography for accurate diagnosis if surgical correction of the lesion is contemplated.