To determine the possible role of atrial natriuretic factor in right ventricular infarction, serial measurements of this hormone were performed in 21 patients with acute inferior myocardial infarction. All patients underwent enzymatic, electrocardiographic, echocardiographic and coronary arteriographic studies. Ten patients also had right heart hemodynamic measurements. Eight patients had evidence of an associated right ventricular infarction (Group I) and 13 patients did not (Group II). Enzymatically estimated infarct size, presence of left heart failure and arrhythmias were similar in both groups. Mean arterial pressure in Group I (72.1 +/- 4.4 mm Hg) was significantly lower (p = 0.02) than in Group II (89.5 +/- 4.6 mm Hg). Seven (88%) of the eight patients in Group I had elevated right atrial pressures and a higher incidence than Group II of prolonged hypotension (75%) and right ventricular dysfunction (75%) clinically and by echocardiography. Plasma atrial natriuretic factor levels (mean values +/- SEM in pg/ml) for days 1, 2, 3 and 7 after infarction were, respectively: 152 +/- 30, 165 +/- 48, 199 +/- 27 and 189 +/- 31 for Group I versus 55 +/- 9, 55 +/- 11, 61 +/- 13 and 77 +/- 20 for Group II. The difference between groups was significant for days 1 (p less than 0.05), 3 and 7 (p less than 0.01) and not significant for day 2 (p = 0.07). These findings show that atrial natriuretic factor elevation is part of the neurohumoral response to right ventricular infarction and are consistent with the hypothesis that atrial natriuretic factor may play a pathophysiologic role in the right ventricular infarct syndrome.