We have examined the effects of erythrocytes on the function and morphology of isolated rat kidneys perfused with a physiological concentration of bovine albumin (45 g/l). (1) In kidneys perfused without red cells, renal vascular resistance (RVR) was low (4.2 +/- 0.3 mm Hg/ml/min/g), fractional sodium excretion (FeNa) was high (14.5 +/- 1.8%) and concentrating ability impaired (maximum urine osmolality 343 +/- 4 mmol/kg). The erythrocyte-free kidney also developed necrosis of the cells of the medullary thick ascending limb (mTAL). (2) Erythrocytes at a hematocrit of 4-6% did not alter RVR but prevented ischemic changes in the mTAL and reduced FeNa to 9.4 +/- 0.03%. Concentrating ability was not improved by a hematocrit of 4-6% despite the presence of a morphologically normal mTAL. (3) At a hematocrit of 40-45%, RVR was increased (to 11.2 +/- 0.4 mm Hg/ml/min/g) and FeNa was further lowered to 3.5 +/- 0.6%. Also, urinary concentrating ability was markedly improved (maximum urine osmolality 640 +/- 35 mmol/kg). (4) The isolated perfused kidney (IPK) at a hematocrit of 40-45% was able to autoregulate renal perfusate flow rate of GFR but autoregulation was incomplete. A 50% increase in perfusion pressure from 100 to 150 mm Hg increased renal perfusate flow rate and GFR 27 and 29%, respectively. Thus the IPK is not able to autoregulate as efficiently as the kidney in vivo, even in the presence of red cells at a normal hematocrit.