Since 1901, more than 20 distinct blood group systems have been identified and characterized. Yet, the ABO System, the first described, remains the most clinically significant in blood transfusion and organ transplantation medicine. The ABO antigens are the only cellular antigens which consistently produce a potent, naturally occurring antithetical antibody which circulates in the plasma of healthy individuals. ABO antigens are expressed on most blood cells, organs, and tissues and in most body fluids. Expression of the antigens results from the interaction of several separate, but closely related genes: ABO, H, and Secretor (Se). Blood group specificity depends upon the inheritance of the ABO and H genes, and the subsequent expression of these antigens on the red blood cells. The "D" or Rho antigen is the most clinically significant blood group antigen next to the ABO antigens. The D antigen belongs to the Rh System, which consists of a trio of genes that are so closely linked that they are inherited as a package. The antigens are an integral part of the red blood cell membrane. They lend stability to the membrane structure when they are normal, but result in decreased red cell survival when absent. Rh antibodies are immune antibodies requiring a stimulus and can cause significant transfusion and childbearing complications if present.