We examined the effects of complement activation on the biological responses of cellulose acetate (CA) beads. Peripheral blood containing the complement activation inhibitor nafamostat mesilate (NM) or heparin was incubated with CA beads in vitro. Thereafter, the fraction of adsorbed granulocytes as well as the generation of complement activation fragments (C3a and C5a) and interleukin 1 receptor antagonist (IL-1ra) were measured. Granulocyte adsorption, complement activation, and IL-1ra release were significantly inhibited in the presence of NM. Adsorption was significantly increased onto CA beads pretreated with plasma containing heparin even in the presence of NM and adding C3a or C5a enhanced IL-1ra release. These results suggested that bound complement fragment (e.g., C3b) on CA beads plays a central role in granulocyte adsorption to CA beads and that C3a and C5a augment the release of anti-inflammatory substances. We therefore conclude that complement activation is involved in these biological responses of leukocyte apheresis.