In terms of blood transfusion, the Rh system is the second most important system after ABO. It is also arguably the most complex (polymorphic) blood group system in humans. Fortunately, at the level of routine blood banking, five antigens account for most work: D, C, E, c, and e.

This module covers the Rh system at a basic level and focuses on clinical aspects of the system.


Credit for discovering the Rh system in 1939-40 is shared by several workers, most notably Landsteiner, Weiner, Levine, and Stetson. Earlier in 1930 Landsteiner had been awarded the Nobel Prize in physiology and medicine for his discovery of ABO in 1900.

In 1940 Landsteiner and Wiener injected the red cells of Rhesus monkeys into rabbits and guinea pigs who made an antibody against the monkey red cells. The rabbit antibody was then tested against the red cells of white residents of New York city and it agglutinated 85% of this population. In honour of the monkey, these people were called Rh positive. Today the term Rh positive refers to people whose red cells have the D antigen, the most important antigen in the system. It is probable that the rabbit antibody was not anti-D, but rather anti-LW (named in honour of Landsteiner and Wiener), an antibody directed against the high frequency LW antigen which is present in a strong form on D-positive cells, and in a weak form on D-negative cells.

Earlier in 1939, Levine and Stetson had discovered an antibody that caused hemolytic disease of the newborn (HDN), which was actually anti-D. Thus, they share credit for discovery of the Rh system. See Pioneers for a tribute to Dr. Levine by the American Society of Clinical Pathologists (ASCP).


After ABO, the Rh system is the second most important system. This is because the D antigen is extremely immunogenic. It causes the production of anti-D in 50 - 70% of Rh(D) negative people who are exposed to the D antigen. (In comparison, most other blood group antigens are only poorly immunogenic, as shown by the fact at only about 1 - 2% of hospital patients have irregular antibodies.) Moreover, anti-D is the most common cause of severe HDN and can cause in utero death. Because of this, in blood transfusion, the patient and donor are matched for Rh(D) type as well as ABO groups.