The invention describes a method to inhibit inflammatory reactions in vivo, more specifically the activation of the complement system. The invention consists of the identification and inhibition of a novel functional domain on the native third component of complement, C3, which domain is essential for the activation of C3. Inhibition of conformational changes of the identified domain prevents the activation of C3, and hence the generation of biologically active peptides such as C3a and C5a, and the formation of membrane attack complexes. The preferred inhibitor is a monoclonal antibody (mAb), a humanised monoclonal antibody or a human monoclonal antibody against the identified domain, or functional fragments derived therefrom, or peptides complementary to the identified domain