To check whether in vivo EDTA prevents complement activation resulting from blood contact with the dialyzer membrane, sham hemodialysis (HD) was performed in seven healthy volunteers using Cuprophan hollow-fiber dialyzers. Blood samples were drawn from the arterial and venous blood lines of the dialyzer before and after EDTA was infused into the arterial line. Venous line plasma C3a concentrations before EDTA infusion were significantly higher than after EDTA. Also, venous line plasma C3a concentrations before and after EDTA infusion were significantly higher than in the arterial line. These results indicate that complement activation can be attenuated by EDTA during sham HD. Technical improvements in the procedure may permit complete inhibition of complement activation.