In uremia there is a marked elevation of serum levels of indoxyl sulfate due to its decreased renal clearance. Indoxyl sulfate is synthesized in the liver from indole which is produced by bacteria in the intestines. To determine the role of indoxyl sulfate in the progression of chronic renal failure, we administered indole, the precursor of indoxyl sulfate, to subtotally nephrectomized uremic rats. The oral administration of indole increased the serum levels of creatinine and blood urea nitrogen and decreased creatinine, inulin, and p-aminohippuric acid clearances. The glomerular sclerosis index in the indole-treated rats was higher than in the control uremic rats. After oral administration, indole could not be detected in the urine, but large amounts of its metabolite, indoxyl sulfate. Thus, indole administration stimulated glomerular sclerosis in a uremic model through the production of indoxyl sulfate.