The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantitation of receptors was performed by computerized in vitro autoradiography with 125 I-labeled α-rat ANP (1-28) as the radioligand. When compared with controls, rats with myocardial infarction had markedly elevated plasma immunoreactive ANP concentrations (462 ± 82 versus 124 ± pg/ml, p < 0.01) and reduced densities of ANP binding in the inner renal medulla (2.93 ± 0.19 versus 3.53 ± 0.22 fmol/mg protein, P < 0.01). Extensive myocardial infarction was associated with a significant decrease in receptor numbers of the inner medulla (33.6 ± 5.7 versus 95.6 ± 9.6 fmol/mg protein, p < 0.01) without significantly altering the affinity constant (1.76 ± 0.51 versus 1.03 ± 0.15 x 10 9 M -1 , p > 0.05). Right ventricular weight increased in proportion to infarct size (r = 0.71, p < 0.01), and both were correlated with plasma immunoreactive ANP levels (r = 0.74, p < 0.01 and r = 0.75, p < 0.01, respectively). Binding densities in the inner medulla of rats with infarcts were negatively correlated with right ventricular weight, plasma immunoreactive ANP concentrations, and also with infarct size (r = -0.92, p < 0.001; r = -0.78, p < 0.001; r = -0.77, p < 0.01, respectively). These results suggest that specific binding sites of ANP in the inner medulla decrease in proportion to the elevation in circulating ANP levels, which in turn are related to infarct size and degree of ventricular dysfunction. Decreased ANP binding sites in the kidney may contribute to the blunted natriuretic response to infused ANP in heart failure and may be responsible in part for the impaired sodium and water excretion in chronic heart failure.