Chronic sodium depletion has been reported to decrease ejection fraction in anesthetized dogs. We tested the hypothesis that this reduction in cardiac performance is due to either hemodynamic or humoral factors. Seven mongrel dogs were fed a low sodium diet (less than 2 mEq Na+ per day) for 5 weeks. Echocardiographic and radionuclide techniques were used to monitor cardiac function. There was a gradual but significant (p less than 0.01) decrease in ejection fraction from 61 +/- 7% (SD) at baseline to 47 +/- 8% after 5 weeks of sodium depletion in association with a fall in left ventricular end-diastolic volume. Ejection fraction did not change in five control dogs fed 55 mEq Na+ per day throughout the 5-week follow-up period. Myocardial contractility did not change in either salt-depleted or control dogs. Plasma norepinephrine levels in the coronary sinus were twice as high in salt-depleted as in control dogs, but there were no significant differences in arterial norepinephrine concentration between the two groups. Therefore, we concluded that reduced ejection fraction during sodium depletion resulted from hemodynamic changes (decreased preload). The excess available norepinephrine failed to increase myocardial contractility, suggesting a dysfunction at the cardiac adrenergic neuroeffector junction.