A synthetic atrial natriuretic peptide (ANF) has been administered to 7 patients with chronic renal failure to evaluate the role of ANF in the regulation of blood volume. ANF (2 micrograms/min) was infused for 60 minutes before hemodialysis and blood pressure, heart rate, plasma proteins and hematocrit were measured at regular intervals. Although a slight decrease in blood pressure occurred during ANF infusion, no significant changes in hematocrit and plasma proteins were observed. These results suggest that administration of exogenous ANF does not modify the volume distribution in patients with chronic renal failure. ANF's lack of effect is perhaps due to the chronic hypervolemia and the high plasma levels of endogenous ANF commonly found in these patients.