The Rh blood group system is one of forty-five known human blood group systems. It is the second most important blood group system, after the ABO blood group system. The Rh blood group system consists of 49 defined blood group antigens, among which the five antigens D, C, c, E, and e are the most important. There is no d ('lower case') antigen. Rh(D) status of an individual is normally described with a positive or negative suffix after the ABO type (e.g., someone who is A Positive has the A antigen and the Rh(D) antigen, whereas someone who is A Negative lacks the Rh(D) antigen). The terms Rh factor, Rh positive, and Rh negative refer to the Rh(D) antigen only. Antibodies to Rh antigens can be involved in hemolytic transfusion reactions and antibodies to the Rh(D) and Rh(c) antigens confer significant risk of hemolytic disease of the fetus and newborn. The Rh blood group system is one of forty-five known human blood group systems. It is the second most important blood group system, after the ABO blood group system. The Rh blood group system consists of 49 defined blood group antigens, among which the five antigens D, C, c, E, and e are the most important. There is no d ('lower case') antigen. Rh(D) status of an individual is normally described with a positive or negative suffix after the ABO type (e.g., someone who is A Positive has the A antigen and the Rh(D) antigen, whereas someone who is A Negative lacks the Rh(D) antigen). The terms Rh factor, Rh positive, and Rh negative refer to the Rh(D) antigen only. Antibodies to Rh antigens can be involved in hemolytic transfusion reactions and antibodies to the Rh(D) and Rh(c) antigens confer significant risk of hemolytic disease of the fetus and newborn. The term 'Rh' was originally an abbreviation of 'Rhesus factor.' It was discovered in 1937 by Karl Landsteiner and Alexander S. Wiener, who, at the time, believed it to be a similar antigen found in rhesus monkey red blood cells. It was subsequently learned the human factor is not identical to the rhesus monkey factor, but by then, 'Rhesus Group' and like terms were already in widespread, worldwide use. Thus, notwithstanding it is a misnomer, the term survives (e.g., rhesus blood group system and the obsolete terms rhesus factor, rhesus positive, and rhesus negative – all three of which actually refer specifically and only to the Rh D factor and are thus misleading when unmodified. Contemporary practice is to use 'Rh' as a term of art instead of 'Rhesus' (e.g., 'Rh Group,' 'Rh factors,' 'Rh D,' etc.). The first rhesus blood type was discovered in 1937 by Landsteiner and Wiener, who named it after a similar factor found in rhesus monkey blood. The significance of the discovery was not immediately apparent and was only realized in 1940, after subsequent findings by Philip Levine and Rufus Stetson. The serum that led to the discovery was produced by immunizing rabbits with red blood cells from a rhesus macaque. The antigen that induced this immunization was designated by them as Rh factor to indicate that rhesus blood had been used for the production of the serum. In 1939, Phillip Levine and Rufus Stetson published in a first case report the clinical consequences of non-recognized Rh factor, hemolytic transfusion reaction, and hemolytic disease of the newborn in its most severe form. It was recognized that the serum of the reported woman agglutinated with red blood cells of about 80% of the people although the then known blood groups, in particular ABO were matched. No name was given to this agglutinin when described. In 1940, Karl Landsteiner and Alexander S. Wiener made the connection to their earlier discovery, reporting a serum that also reacted with about 85% of different human red blood cells. In 1941, Group O: a patient of Dr. Paul in Irvington, NJ, delivered a normal infant in 1931: this pregnancy was followed by a long period of sterility. The second pregnancy (April, 1941) resulted in an infant suffering icterus gravis. In May 1941, the third anti-Rh serum (M.S.) of Group O became available. Based on the serologic similarities, Rh factor was later also used for antigens, and anti-Rh for antibodies, found in humans such as those previously described by Levine and Stetson. Although differences between these two sera were shown already in 1942 and clearly demonstrated in 1963, the already widely used term 'Rh' was kept for the clinically described human antibodies which are different from the ones related to the rhesus monkey. This real factor found in rhesus macaque was classified in the Landsteiner–Wiener antigen system (antigen LW, antibody anti-LW) in honor of the discoverers. It was recognized that the Rh factor was just one in a system of various antigens. Based on different models of genetic inheritance, two different terminologies were developed; both of them are still in use. The clinical significance of this highly immunizing D antigen (i.e., Rh factor) was soon realized. Some keystones were to recognize its importance for blood transfusion (including reliable diagnostic tests), hemolytic disease of the newborn (including exchange transfusion), and very importantly the prevention of it by screening and prophylaxis.