In contrast to most renal vasodilators, such as acetylcholine (ACh), secretin increases renal blood flow in the dog without a marked effect on sodium excretion (UNaV). To investigate this observation, we studied the relationship between renal vasodilation, UNa»V, and papillary plasma flow (PPF) in rats, infused either with ACh or secretin into the aorta at the level of both renal arteries. ACh significantly increased GFR, PAH clearance, and UNaV (Δ + 0.35 ml/min, + 2.11 ml/min and + 1.77 /iEq/min, respectively;P< 0.05). PPF rose from 50 ± 2.6 ml/min 100 g (mean ± SE) in control rats to 91 ± 4.7 ml/min 100 g after ACh (P< 0.001). Despite a similar increase in PAH clearance after secretin (+ 2.21 ml/min; P< 0.01), UNaV remained unchanged and PPF was only slightly, although significantly, increased (from 50 ± 2.6 ml/min 100 g to 65 ± 2.75 ml/min 100 g;P< 0.05). Both total kidney and papillary vasodilation, and the increase in UNaV after ACh were blocked by previous administration of meclofenamate (M), a prostaglandin inhibitor. No effect of M in secretin-infused rats was observed. In conclusion, the relationship between total renal vasodilation and natriuresis was dissociated with secretin, but not with ACh. However, a relationship between the natriuresis and influence on papillary hemodynamics was observed with both vasodilators. Finally, the renal hemodynamic and natriuretic effects of ACh are probably mediated by prostaglandin release.Circ Res 47: 839-844, 1980