The antigens of the Cromer blood group system are located on the protein decay-accelerating factor (DAF). This system consists of ten high-prevalence and three low-prevalence antigens; the molecular basis for all of these antigens is a single nucleotide polymorphism in the DAF gene. DAF is a 70,000-Da plasma membrane protein that is widely distributed on all blood cells and on endothelial and epithelial tissues. The physiological role of DAF is to inhibit the complement cascade at the level of the critical C3 convertase step. By this mechanism,DAF acts to protect autologous cells and tissues from complement-mediated damage and hence can play a role in preventing or modulating autoimmune disease and inflammation. The use of recombinant DAF as a therapeutic agent in autoimmunity and inflammation, and of DAF transgenic animals in xenotransplantation, is being actively investigated. Additionally, DAF serves as a receptor for certain strains of Escherichia coli and certain types of enteroviruses. The DAF protein that contains the Cromer antigens serves important roles in health and disease.