The contribution of alterations in renal hemodynamics to the diuretic and natriuretic actions of atrial natriuretic factor (ANT) was studied in chronically instrumented conscious dogs. Injection of ANF-(99–119), 10 μg/kg, had no effect on mean arterial pressure, heart rate, renal blood flow, or calculated renal vascular resistance; However, it increased urine flow rate (86 ± 20%) and sodium (118 ± 24%) and potassium (35 ± 22%) excretion (p< 0.05). In contrast, ANF-(99–122), 10 /ig/kg, significantly increased renal blood flow (26 ± 4.5%), reduced renal vascular resistance (24 ± 2.9%) and arterial pressure (5.5 ± 1.9%), and markedly increased urine flow rate (198 ± 34%) and sodium (206 ± 32%) and potassium (75 ± 27%) excretion (p< 0.05), being almost twice as effective in the first 10 minutes as was ANF-(99–119) infusion. During a brief infusion, ANF-(99–122) (10 fig/ kg/min for 4 minutes) increased renal blood flow (24 ± 2.7%), heart rate (18 ± 5.7%), urine flow rate (199 ± 25%), and sodium (290 ± 81%) and potassium (104 ± 17%) excretion. Injection of radioactive microspheres (15 or 9 μm) to measure intrarenal distribution of blood flow during the steady state increase in renal blood flow indicated that ANF-(99–122) infusion preferentially increased outer cortical blood flow. Blood flow in the four zones of the kidney cortex (Zone 1, outer, and Zone 4, inner) increased 96 ± 25% (Zone 1), 199 ± 87% (Zone 2), 139 ± 47% (Zone 3),p< 0.05, and 25 ± 28% (Zone 4,p= NS). Infusion of ANF-(99–119) did not lead to a redistribution of renal cortical blood flow as seen with ANF-(99–122). During a 1-hour infusion of ANF-(99–122), renal blood flow increased only transiently whereas glomerular filtration rate, urine flow rate, and sodium and potassium excretion increased 118 ± 15%, 104 ± 6.8%, 144 ± 24%, and 115 ± 26%, respectively. Following α-adrenergic receptor blockade, infusion of ANF-(99–122) resulted in renal vasodilation for the duration of the study. Therefore, In conscious dogs, ANF-(99–119) and ANF-(99–122) both enhance renal function while ANF- (99–122) also increases renal blood flow. Although not essential, the ANF-induced renal vasodilation accentuates and hastens the initial diuresis and natriuresis, thereby increasing the total salt and water excretion.