Factor D, an essential enzyme of the alternative pathway (AP) of complement, accumulates in end-stage renal failure (ESRF). Polyacrylonitrile (PAN) membrane activates complement poorly and has been shown to adsorb C3a, the main anaphylatoxin released during complement activation. In the present work we investigated whether factor D might be adsorbed on PAN. In vitro there was a loss of hemolytic factor D when normal human serum (NHS) was incubated with PAN dialysis fibers, whereas no loss was observed with cuprophan (Cu) fibers. There was a dose and time dependent binding of purified radiolabeled factor D to PAN but not to Cu. The hemolytic function of factor D released from PAN by 2 M NaCl was normal. By contrast, factor D was inactive while adsorbed to PAN fibers. When 50 ml of NHS or 100 ml of whole blood were passed through a new hollow fiber PAN dialyzer 95% of factor D was adsorbed. The eluate from a PAN filter which had been used for dialysis in a patient with ESRF contained 38.4 mg of hemolytic factor D, representing 34% of the proteins eluted. By immunoblotting, antigenic factor D from the PAN eluate was identical to purified human factor D. In six patients there was a 81.4% decrease in hemolytic factor D in blood after dialysis with PAN, contrasting with a 9.6% decrease in those dialyzed with cellulose acetate. No factor D was found in the dialysis fluid of PAN dialyzers, indicating that PAN removed factor D mainly by adsorption. In conclusion, PAN has a significant capacity to adsorb factor D, a reaction that might contribute to the diminished capacity of PAN membrane to activate the AP of complement. Whether the efficient removal of large amounts of factor D might be beneficial in uremic patients remains to be defined.