The hematocrit was increased acutely in anesthetized dogs by means of an isovolemic exchange transfusion in which packed red cells from a donor dog were infused in exchange for an equivalent volume of whole blood. Renin release by the kidney increased three- to eightfold in response to a 20% rise in hematocrit. No increase in renin release occurred when the exchange transfusion was performed with reconstituted blood having the same hematocrit as the dog's own blood. The increase in hematocrit caused a decrease in p-aminohippurate clearance (77 to 48 ml/min) and sodium excretion (223 to 85 μequiv/min) but caused no change in mean arterial pressure or glomerular filtration rate. The results suggested that changes in the rheological properties of blood provide a potent stimulus for renin release by the kidney.