There is increasing clinical interest in improving blood rheology to optimize organ function, but studies correlating the two are scarce. To study this, rat kidneys were perfused in vitro at 37 degrees C at a constant mean renal arterial pressure of 160 mm Hg. The perfusate consisted of an oxygenated Krebs HCO3 buffer containing 1 mg/ml glucose, 0.5 mg/ml creatinine, amino acids, [3H]inulin (marker for GFR), 2.5 g/dl albumin, and 10 or 20% hematocrit. In some experiments, RBC were made nondeformable by heating at 50 degrees C for 20 min. Deformability was measured by an ektacytometer. In other experiments, 0.001% of an anionic polyacrylamide (Separan), a drag-reducing agent, was added to the perfusate. Viscosity was measured with a cone and plate viscometer, [Na+] with a flame spectrophotometer, and perfusate flow with a Brooks in-line flowmeter. Other functional parameters, GFR, urine flow, RPF, and reabsorption of sodium and water, were also measured. The results indicate that (1) making RBC nondeformable or increasing viscosity by increasing hematocrit reduces renal function, and (2) addition of a drag-reducing agent improves renal function at 20% hematocrit. We conclude that rheologic manipulation of a perfusate solution can alter flow and renal function.