Her body reacts by forming anti-Rh agglutinins in future pregnancies these may diffuse back through the placental membrane into the fetal circulation and cause clumping of the fetal erythrocytes. The Rh antigens (agglutinogens) in the fetal tissues diffuse through the placental membrane at birth and enter the mother's blood.

In pregnancy difficulty may arise when the mother is Rh negative and the fetus is Rh-positive. Thus there may be no difficulty in the first transfusion of Rh incompatible blood, but on repeated exposure to the Rh factor, the Rh-negative individual becomes “sensitized” to the agglutinogens in Rh positive blood and builds up a greater quantity of antibodies. It should be pointed out that this immune reaction does not occur immediately, but depends on the gradual formation of antibodies the response also is more severe in some persons than in others. This agglutination is an immune reaction and depends on the formation of antibodies against the specific agglutinogen (Rh factor) present on the erythrocytes and in transfused blood. The presence or absence of an Rh factor is especially important in blood transfusions because mixing of two types of blood may result in the agglutination (clumping together) of red blood cells, with plugging of the capillaries and destruction of the red blood cells. Approximately 85 per cent of all Caucasian people are Rh positive and 15 per cent are Rh negative other races may have different percentages. If one of these factors is present in an individual's erythrocytes, the blood type is Rh positive (D positive, Rh 0) if the factor is absent the blood type is Rh negative (D negative, dd, or Hr 0 ).

There are at least eight different variations, each being called an Rh factor (named for the rhesus monkey used in early experiments). Genetically determined antigens (agglutinogens) present on the surface of erythrocytes.

Rh factor positive