To investigate whether the response of atrial natriuretic factor (ANF) to volume expansion is impaired in the early stages of dilated cardiomyopathy, the effects of saline load (SL; 0.25 ml/kg. min for 120 min) were assessed in 12 patients with dilated cardiomyopathy and asymptomatic to mildly symptomatic heart failure (HF) and in nine normal subjects (N). SL increased plasma ANF levels in N (from 143±2 to 19.5±3 and 26±4 pg/ml, at 60 and 120 min, respectively, P < 0.001), but not in HF (from 42.9±9 to 45.9±9 and 43.9±8 pg/ml). Left ventricular end-diastolic volume (LVEDV) and stroke volume were increased (P < 0.001) by SL in N but not in HF. Urinary sodium excretion (UNSY) increased in N more than in HF during SL, whereas forearm vascular resistance (FVR) did noi change in N and increased in HF (P < 0.001). In five HF patients SL was performed during ANF infusion (50 ng/kg, 5 ng/kg min) that increased ANF levels from 37.1±10 to 146±22 pg/ml. In this group, SL raised both LVEDV (P < 0.01) and ANF (P < 0.05), whereas FVR did not rise. In addition, the UN.V increase and renin and aldosterone suppressions by SL were more marked than those observed in HF under control conditions. Thus, in patients with dilated cardiomyopathy and mild cardiac dysfunction, plasma ANF levels are not increased by volume expansion as observed in N. The lack of ANF response is related to the impaired cardiac adaptations. The absence ofan adequate increase ofANF levels may contribute to the abnormal responses of HF patients to saline load. (J.