The diuretic-natriuretic responses of eight assay rats to extracts of atrial tissue obtained 3 months after left coronary ligation were less than the responses to extracts of tissue from sham-operated controls. The mean difference in diuresis (sham-operated response minus ligated response) was 370 (range 22 to 656) μl/20 minutes (p < 0.01) and in natriuresis 56 (range -92 to 222) μEq/20 minutes (p = 0.19). The differences in diuretic responses to these extracts was directly related to the severity of elevation of left ventricular end-diastolic pressure in these rats (r = -0.82, p = 0.01). These results in a model with varying degrees of left ventricular dysfunction suggest that myocardial damage is associated with a chronic decrease in atrial natriuretic factor. Reduced circulating atrial natriuretic factor therefore could contribute to the previously observed impaired ability of coronary ligated rats to excrete a saline load and to the sodium retention observed in clinical heart failure. Conclusive evidence will depend on the development of techniques to measure plasma levels of this hormone.