A major endogenous ligand substance, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), accumulated in the sera of uremic patients, inhibited phenytoin binding to pooled serum obtained from healthy subjects and to human serum albumin in a concentration usually observed in the sera of patients with uremia. This suggests that CMPF is a major drug-binding inhibitor present in uremic serum and may be one of the so-called 'uremic toxins'.