The effects of hemodialysis on the levels of serum prealbumin (pA) were studied on a crossover basis in 17 uncomplicated patients. Bicarbonate dialysate was used exclusively, and two different membranes, cuprophane and polysulfone, were compared. We aimed to prove the induction of an acute-phase response during the procedure. Serum pA, corrected for hemoconcentration, decreased significantly 24 h after the start of cuprophane hemodialysis and returned to the initial value within 48 h. No such change was observed using polysulfone membranes. These results were seemingly correlated with the effects of the membranes on complement activation. It is concluded that cuprophane hemodialysis is indeed associated with an acute-phase response, probably due to interleukin-1 release during the treatment, and that the membrane composition has some role in inducing it. Thus, serum pA analysis may prove useful as an indicator of the biocompatibility of the dialysis procedure.