This prospective, randomized controlled study was designed to examine the effects of oral adsorbent AST-120 on the progression of chronic renal failure (CRF) in patients on a strict low protein diet (LPD). Twenty-six patients with CRF (serum creatinine 3.0 to 8.6 mg/dl) on a LPD were randomly assigned to a control group (N = 13) or an AST-120 group (N = 13). The 1/Cr slope and creatinine clearance (CCr) slope were used to estimate the progression rate of CRF; uremic toxins, serum and urinary indoxyl sulfate (IS), peak 2a and guanidino substrates (GS) measured by HPLC. Comparisons were made between the baseline observation period for 6 to 12 months and the treatment period (0.6 g/kg/day of LPD alone or concurrent with 6 g/day of AST-120, for the control and the AST-120 groups, respectively) for 12 to 24 months in both groups. Both the 1/Cr slope and CCr slope were significantly lessened in the treatment period only in the AST-120 group. Serum and urinary IS, but neither peak 2a nor GS were significantly decreased in the treatment period only in the AST-120 group. We conclude that AST-120 administration concurrent with LPD may be superior to LPD alone in retarding the progression of CRF by inhibiting accumulation of indoxyl sulfate.