p-Cresylsulfate, a metabolite of p-cresol, is reported as prototypic protein-bound Uremic toxin, inefficiently removed by haemodialysis. The binding between p-cresylsulfate or p-cresol and human serum albumin was Studied using rnicrocalorimetry. The results confirm that the two molecules are protein-bound. However. the affinity of p-cresylsulfate and p-cresol toward human serum albumin is moderate at 25 degrees C and becomes relatively weak at physiological temperature, 37 degrees C. The binding principally involves van der Waals type interactions, and the binding sites of the two molecules are the same or very close, The low fraction of bound toxin (13-20%) appears to be insufficient to link strong binding to poor removal of this toxin by hemodialysis.