A protamine-coated Cuprophan hemodialysis membrane possessing improved blood compatibility was developed. Protamine was covalently immobilized onto the inner walls of the Cuprophan hollow fibers, using the cyanogen bromide (CNBr) activation method. Studies conducted with aqueous solutions indicated that the immobilization process did not introduce deterioration of the membrane mechanical and mass transfer properties; the permeability of several compounds through the protamine-coated membrane was unchanged. The modified membrane was rendered nonthrombogenic by the adsorption of heparin to the protamine-bound surfaces. Heparin adsorbed on the immobilized protamine retained about 20% of its initial anticoagulant activity. Preliminary studies using the hemolytic complement assay indicated that complement activation by the protamine-coated membrane was statistically far less than that by the untreated membrane.