Sera and EDTA-Plasma of patients with severe Haemophilia A were analysed for immune complexes and the hemolytic activity of complement in relation to Factor VIII replacement, in order to confirm or possibly exclude a relationship to allergic reactions. Immune complexes were isolated by PEG precipitation and quantitated. In addition a solid phase ELISA assay was used to detect complement-binding complexes. Total hemolytic complement activity of the classical and the alternate pathway was measured in addition to the C3 splitproduct C3d. The results obtained from 12 patients with severe Haemophilia A showed slightly increased immune complex titers, no changes of the immune complex levels during Factor VIII replacement and no alteration of the complement system following the infusions. One patient developed an allergic reaction without evidence of complement activation.