Rh factor, protein substance present in the red blood cells of most people, capable of inducing intense antigenic reactions. The Rh, or rhesus, factor was discovered in 1940 by K. Landsteiner and A. S. Wiener, when they observed that an injection of blood from a rhesus monkey into rabbits caused an antigenic reaction in the serum component of rabbit blood (see immunity). When blood from humans was tested with the rabbit serum, the red blood cells of 85% of the humans tested agglutinated (clumped together). The red blood cells of the 85% (later found to be 85% of the white population and a larger percentage of blacks and Asians) contained the same factor present in rhesus monkey blood; such blood was typed Rh positive. The blood of the remaining 15% lacked the factor and was typed Rh negative. Under ordinary circumstances, the presence or lack of the Rh factor has no bearing on life or health. It is only when the two blood types are mingled in an Rh-negative individual that the difficulty arises, since the Rh factor acts as an antigen in Rh-negative persons, causing the production of antibodies. Besides the Rh factor, human red blood cells contain a large number of additional antigenic substances that have been classified into many blood group systems (see blood groups); however, the Rh system is the only one, aside from the ABO system, that is of major importance in blood transfusions. If Rh-positive blood is transfused into an Rh-negative person, the latter will gradually develop antibodies called anti-Rh agglutinins, that attach to the Rh-positive red blood cells, causing them to agglutinate. Destruction of the cells (hemolysis) eventually results. If the Rh-negative recipient is given additional transfusions of Rh-positive blood, the concentration of anti-Rh agglutinins may become high enough to cause a serious or fatal reaction. The same type of immune reaction occurs in the blood of an Rh-negative mother who is carrying an Rh-positive fetus. (The probability of this situation occurring is high if the father is Rh positive.) Some of the infant's blood may enter the maternal circulation, causing the formation of agglutinins against the fetal red blood cells. The first baby is usually not harmed. But, if the mother's agglutinins pass into the circulation of subsequent fetuses, they may destroy the fetal red blood cells, causing the severe hemolytic disease of newborns known as erythroblastosis fetalis.