Inappropriate polyuria leading to hypovolemia and hypotension occurs frequently in severely septic patients. It's etiology was studied in three patients with polyuria and systolic hypotension. Glomerular filtration rate and renal blood flow were measured by the standard renal clearance techniques. Renal blood flow distribution to the outer cortex, inner cortex-outer medulla, and the inner medulla were measured by radioactive xenon. The glomerular filtration rate, renal blood flow, and renal blood flow distribution were normal. Polyuria does not result from a maldistribution of renal blood flow. Antidiuretic hormone did not alter the polyuric syndrome. These data suggest that sepsis produces a blockade at either the distal tubule or the collecting duct, thereby preventing salt and water conservation. This blockade may be due to either a toxin or a toxic metabolic breakdown product of sepsis.