The biologic response to uremia and to the associated chronic inflammation is an active area of research. Among the different modalities developed in the technology field of chronic renal replacement, hemodialfiltration has evolved consistently. On-line production of substitution fluid by 'cold sterilization' of dialysis fluid by ultrafiltration gives access to virtually an unlimited amount of sterile and non-pyrogenic intravenous grade solution. Today, on line HDF is already a widespread, accepted treatment. Here, we will review the main mechanisms through which on line hemodialfiltration acts and the biological response observed in relation to the immune system dysfunction and the anemia associated to chronic kidney disease. Copyright (c) 2007 S. Karger AG, Basel.