The renal response to a selective increase in the Na+ concentration of the blood perfusing the central nervous system was investigated in conscious dogs treated with the converting enzyme inhibitor enalaprilat and the aldosterone antagonist canrenoate. In split-infusion experiments the plasma [Na+] of carotid blood was increased (approx. 6 mM) by bilateral infusion of hypertonic NaC1. Concomitantly distilled water was infused into the v. cava making the sum of the infusions isotonic. In control experiments isotonic saline was infused at identical rates into all three catheters. Na+ excretion increased markedly in both series, 103 +/- 14 to 678 +/- 84 mumol min-1 during split-infusion and 90 +2- 14 to 496 +/- 74 mumol min-1 during the isotonic volume expansion. Peak rate of excretion, peak fractional sodium excretion, and cumulative sodium excretion were all significantly higher (P < 0.05) during split-infusion than during control experiments. Plasma vasopressin increased only during split-infusion (0.68 +/- 0.11 to 2.4 +/- 0.8 pg ml-1) while the increases in plasma atrial natriuretic peptide were similar in the two series. Urinary excretion of urodilatin (ANP95-126) increased significantly more during split-infusion (46 +/- 11 to 152 +/- 28 fmol min-1) than during the isotonic volume expansion (45 +/- 14 to 84 +/- 16 fmol min-1) (P < 0.05). It is concluded that the natriuretic mechanisms activated by a selective increase in the Na+ concentration of carotid blood and associated with increased excretion of urodilatin cannot be eliminated by blockade of the renin-angiotensin-aldosterone system.