T he early pathophysiological changes in acute urate nephropathy were investigated in a rat model using micropuncture, clearance, and morphologic methods. Plasma urate was increased from 1.2 +/- 0.6 to 20.1 +/- 3.1 mg/100 ml (P less than 0.001). Urinary urate rose from 24.3 +/- 5.1 to 142.2 +/- 21.0 mg/100 ml (P less than 0.001). Renal plasma flow and glomerular filtration rate fell to 17 and 14% of control values, respectively, and urine flow rate decreased from 11.3 +/- 4.8 to 4.2 +/- 2.2 mul/min (all P less than 0.005) Superficial nephron filtration rate fell less than that of the whole kidney (70 vs. 86%). Both proximal and distal tubular pressures were increased from 10.6 to 26.1 mm Hg and from 7.2 to 24.7 mm Hg, respectively (P less than 0.005). Efferent arteriolar and peritubular capillary pressures were increased twofold. Vascular resistance beyond the peritubular capillaries increased from 4.8 X 10(9) to 21.6 X 10(9) dynes s/cm5. Extensive deposits of uric acid and urate were found in the tubular system and vasa recti from the corticomedullary junction to the tip of the papilla. It is concluded from these experiments that not only tubular obstruction in the collecting ducts, but also obstruction of the distal renal vasculature, are the primary early pathogenetic events in acute urate nephropathy.