To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction.