Improvement of the blood-compatibility of the polyhydroxyethylmethacrylate (PHEMA) microcarriers is attempted. PHEMA microspheres were prepared by a suspension polymerisation technique and activated by CNBr in an alkaline medium (pH 11.5). In order to improve the blood-compatibility of the PHEMA microspheres, heparin was immobilized onto these microspheres. Albumin adsorption onto PHEMA and heparin immobilized PHEMA microspheres was obtained at different experimental conditions. PHEMA and heparin immobilized PHEMA microspheres were contacted with blood in in-vitro systems and in ex-vivo animal experiments. Selective protein adsorption, conformational changes in blood proteins, loss of blood cells, clotting times, and other hematological properties were followed. The increase in the initial concentrations of both CNBr and heparin caused an increase in the amount of heparin immobilized onto PHEMA microspheres, and also caused higher adsorption of BSA. Fibrinogen was the highest adsorbed protein onto PHEMA/heparin microspheres. Preadsorption of BSA onto PHEMA/heparin microspheres made a passivation effect. PHEMA/heparin microspheres did not cause any significant conformational changes in blood proteins. Anticoagulant effect of the immobilized heparin was clearly observed with coagulation experiments. Loss of cells in the blood contacting with PHEMA/heparin microspheres was significantly lower than that observed with PHEMA microspheres.