In 1939, Levine & Stetson first described the case of a mother, after giving birth to a stillborn child, having a haemolytic transfusion reaction following transfusion her husband’s blood. Her serum agglutinated her husband’s red cells and those of 80% of ABO-compatible donors. In 1940, Landsteiner & Wiener injected Rhesus-monkey red blood cells into rabbits. The rabbit serum agglutinated Rhesus-monkey red cells, and also 85% of human red cells. They called this antibody anti-Rh, and in 1941 Levine & Stetson’s human antibody was shown to have the same pattern of reactivity as the rabbit anti-Rh antibody. However, by 1942, Fisk & Foord had demonstrated a difference between rabbit and human anti-Rh: red cells from all newborn babies, whether Rh positive or negative as defined by human anti-Rh were positive with the rabbit anti-Rh. In 1963, Levine et al . finally proved that human and rabbit anti-Rh did not react with the same antigen. However, owing to common usage of the term, ‘Rh’ was kept as the title for the human antibodies. The rabbit ‘anti-Rh’ was then called anti-LW in honour of Landsteiner & Wiener. Even today people often make the mistake of referring to the ‘Rhesus’ blood group system; this is incorrect, as the blood-group antigen has nothing to do with Rhesus monkeys, and should be referred to as the ‘Rh’ blood group system. In 1943, Wiener demonstrated the presence of six alleles in the Rh system with three different antisera, and since then the system has been shown to have many further variants and complexities. In 1953, it was discovered that some RhD-positive individuals can make anti-D, and this led to the hypothesis that the RhD antigen is a complex antigen comprised of a series of epitopes. A lack of part of the antigen means that an individual can make antibody to this part. In 1942, Levine confirmed that Rh incompatibility between mother and fetus was the major cause of haemolytic disease of the newborn (HDN). Various studies showed that, depending on the population, 3–25% lack the Rh antigen D, and that RhD-negative individuals readily make anti-D. RhD is thus of critical importance in blood transfusion, and all transfusions are routinely matched for RhD compatibility. In emergency situations RhD-negative blood is given, particularly if the recipient is a female of child-bearing age, to avoid immunization. RhD-negative women can be treated with prophylactic anti-D to prevent HDN. Although the mechanism of action for this process is not fully understood, it is apparent that rapid clearance of fetal red cells from the maternal circulation by passively administered anti-D prevents the mother making immune anti-D. A very successful programme of routine postdelivery administration of anti-D to RhD-negative mothers bearing RhD-positive babies has greatly reduced the incidence of HDN. However, some fetal cells can also enter the maternal bloodstream during pregnancy, and cause immunization. To prevent this cause of HDN, routine antenatal administration of anti-D is now being adopted in many countries.