ABSTRACTTo evaluate the relationship between plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH) and different hemodynamic parameters in man, we studied 34 patients undergoing right heart catheterization. Plasma levels of IR-ANH in blood samples withdrawn from the femoral vein (n = 28), right ventricle (n = 27), and left ventricle (n = 17) were determined by radioimmunoassay. Right atrial pressure, pulmonary arterial wedge pressure, heart rate, and mean arterial pressure were found to be independent and significant predictors of IR-ANH plasma levels. The closest correlations were between right atrial pressure and either right ventricular IR-ANH levels (r = .78, p > .001) or femoral vein IR-ANH levels (r = .52, p < .006). Five patients with isolated left ventricular failure had elevated IR-ANH levels out of proportion to their right atrial pressure levels. Pulmonary arterial wedge pressure also correlated with right ventricular IR-ANH levels (r = .46, p < .002) and with femoral vein IR-ANH levels (r = .58, p < .002). A single patient with isolated right heart failure had markedly elevated IR-ANH levels despite normal pulmonary arterial wedge pressure. Right ventricular levels were twice femoral vein levels and were closely correlated (181 + 40 vs 90 + 20 pmol/liter; r = .90, p < .001). Right ventricular and left ventricular levels were almost identical (155 + 46 vs 146 43 pmol/liter; r = .99, p < .001). Patients with volume overload states had elevated IR-ANH levels. We conclude that distention of either atrium may act as a potent stimulus for IR-ANH release in man, although circulating levels may be clinically ineffective in producing diuresis and natriuresis. Further investigations into the mechanisms that regulate IR-ANH secretion in man should include atrial pressure measurements.