We previously showed that the extent of infarction is virtually identical in patients with anterior and inferior infarction despite the more favorable prognosis associated with the latter. We postulated that the damage associated with inferior infarction is shared by both ventricles, thereby causing less hemodynamic impairment than anterior infarction, which involves only the left ventricle. To further explore this hypothesis, global and regional function of both right and left ventricles was assessed by gated radionuclide ventriculography in 50 patients with infarction within 48 hours after admission and gain on the tenth day. Radionuclide ventriculography was also performed in 10 normal subjects. In 22 patients who had anterior infarction, the mean global left ventricular ejection fraction was decreased (27±15% [±SD] vs 64±10% in normal subjects, p<0.05), reflecting regional abnormalities, and increased only slightly by the tenth day (33±11%, p<0.05). The global right ventricular ejection fraction was decreased (28±11% vs 43±9% in normal subjects, p<0.05), reflecting a uniform depression of function without localized abnormalities, and returned to normal by the tenth day (43±12, p<0.05). In 20 patients who had inferior infarction, global left did not change (55±10). In contrast, global right ventricular ejection fraction was severely and persistently decreased (23±9 vs 29±9, p>0.05). In 20 patients who had inferior infarction, global left ventricular ejection fraction was only slightly decreased (51±11%), reflecting inferoapical dysfunction, and did not change (55±10). In contrast, global right ventricular ejection fraction was severely and persistently decreased (23±9 vs 28±9, p>0.05), reflecting abnormalities primarily of the inferior region. The decreased right ventricular ejection fraction after inferior infarction correlated inversely with enzymatic estimates of infarct size (r=-0.85, p>0.01), although there was no correlation between left ventricular ejection fraction and infarct size. Thus, the functional responses of the ventricles to myocardial infarction are markedly influenced by the site of damage. In patients with anterior infarction there was persistent regional and global impairment of left ventricular function but only transient impairment of the right ventricle, whereas inferior infarction was associated with severe, persistent regional and global impairment of the right ventricle. These results indicate that the site of infarction is a major determinant of ventricular function and its recovery and that right ventricular infarction is much more common with inferior infarction than is generally appreciated.