Most renal vasodilators are natriuretic. However, secretin increases renal blood flow (RBF) markedly but produces only a very slight increase in sodium excretion (UNaV). To investigate this observation further, the relationship between vasodilatation, interstitial pressure (IP), and UNaV was studied in dogs. Intrarenal infusion of secretin increased RBF (delta=107+/-19 ml/min). The IP, as measured from chronically implanted polyethylene matrix capsules, was not significantly changed (delta=-0.3+/-0.5 mmHg). UNaV was slightly, although significantly, increased (delta=19+/-4 mueq/min). Following a similar increase in RBF with an intrarenal infusion of acetylcholine (ACh), IP and UNaV increased markedly (delta=8.2+/-0.8 mmHg and 174+/-23 mueq/min, respectively). Neither secretin nor ACh) altered glomerular filtration rate or blood pressure. Both secretin and ACh produced comparable increases in peritubule capillary(delta=5+/-1 and 7.5+/-1.4 mmHg, respectively) and free-flow tubule pressure (delta=7+/-2 and 9.5+/-1.4 mmHg, respectively). In summary, the usual relationship between vasodilatation and IP was dissociated during secretin infusion, whereas the relationship between IP and natriuresis was not dissociated.