We have previously demonstrated that chemical modification of cellulosic membranes with dimethyl-amino-ethyl (DEAE) groups significantly improves membrane properties in terms of biocompatibility. Here, we show that DEAE substitution also alters the membrane's thrombogenic properties, and cellulosic membranes with various amounts of DEAE substitution were produced. Clinical dialyzers were constructed using two experimental membrane materials: modified cellulose-low (MC-low) and MC-high; standard unsubstituted cellulose was used as a control. Six patients were treated for a period of 3 weeks with each type of dialyzer and a heparin dose of less than 6000 IU/treatment. MC-low exhibited less extracorporeal beta-thromboglobulin and thromboxane B2 release than MC-high or Cuprophan. In addition, residual blood volume after clinical use was lower in the MC-low type. MC-low and MC-high induced less complement activation than Cuprophan, as characterized by extracorporeal C5a and C3a plasma concentrations (75% less C5a generation and 50 to 70% less C3a generation than unsubstituted cellulose).