The present experiments were performed to clarify the renal and hemodynamic effects of atrial natriuretic peptide (ANP) in dogs with chronic renal failure (CRF; produced by 5/6 nephrectomy 3-4 weeks before study). Synthetic alpha-hANP was administered intravenously (0.1 micrograms/kg body weight for 30 min) with a priming bolus injection (1.0 micrograms/kg body weight) to anesthetized controls (n = 8) and CRF-dogs (n = 10). The effects of ANP on renal function, cardiac function, lithium clearance, and plasma ANP levels during clearance studies were determined. Effects of ANP on the hemodynamics were observed to the same degree in both groups. An increase in inulin clearance (CIn) was noted only in the CRF-dogs (7.5 +/- 2.1 to 9.6 +/- 2.9 ml/min; p less than 0.01). The infusion of ANP increased the urine volume, absolute sodium excretion, and osmolar clearance in the control and CRF groups. The fractional excretion of lithium (FELi), a marker of the proximal reabsorption of sodium, was higher at baseline in the CRF group (control group, 24.4 +/- 6.7 vs. CRF group, 41.5 +/- 13.2%; p less than 0.001). Following ANP infusion, FELi increased in both groups. The plasma ANP levels were monitored during the clearance study, and those of the CRF group were higher throughout the experiments. Thus, extrinsic ANP induced diuresis and natriuresis in CRF-dogs, produced by nephron mass reduction. Discrepancies in the pattern of response and plasma ANP levels were observed between the controls and CRF-dogs, suggesting that the action and metabolic clearance rate of ANP were altered in the CRF state.