The interactions between blood and the dialysis membrane, aside from solute clearance, can be referred to as biocompatibility. It has increasingly been recognized that significant side effects may occur as a result of interactions of blood with the dialysis membrane itself. The use of unmodified cellulosic hemodialysis membranes results in potent activation of the alternative pathway of complement, and numerous investigators have now carefully defined the membrane characteristics that contribute to complement activation, adsorption, and clearance. Complement-dependent granulocyte activation during hemodialysis causes neutrophil degranulation and protease release, the production of reactive oxygen species, and modulation of granulocyte cell adhesion molecules. Recently, a number of experimental studies in animal models suggest that complement and granulocyte activation during hemodialysis could contribute to the prolongation of acute renal failure. Based on the hypothesis that hemodialysis with complement and granulocyte-activating membranes could contribute to the prolongation of acute renal failure and increased mortality, several recent prospective randomized clinical trials examining the role of membrane biocompatibility in the treatment of acute renal failure have been reported. Although not unanimous in their conclusions, most studies suggest that hemodialysis with more biocompatible membranes in patients with acute renal failure leads to a more rapid return of renal function and a lower morbidity and mortality. Thus, hemodialysis membrane biocompatibility may be an important contributor to the outcome of patients with acute renal failure who require dialysis.