In 1965 McCormick, Francis and Gelb described an antibody in the serum of an African-American prenatal patient. Since the patient's red cells typed as Go(a+) they believed the antibody was anti-Go^b. However, ten years later Stroup and McCreary reported four additional examples of the antibody and demonstrated that it could not be part of the Rh system and was not anti-Go^b. Thus the antibody was renamed anti-Cromer (Cr^a) after the first antibody producer. To date, the majority of these antibodies have been found in Blacks and are often stimulated by pregnancy.

Additional antigens and antibodies were soon discovered for this system, some of which showed distinct ethnic differences. The antibody to the high frequency antigen known as Tc^a was first found in two Black females. Indeed, its low frequency partner was found in 5% of Blacks but not in Caucasians. In the later group, another low incidence partner was found which was named Tc^c. A new antibody related to Cromer was reported by Levene and named anti-Dr^a. Several examples of Dr(a-) have been found almost exclusively in Israeli Jews originating from the Bukharan area of Uzbekistan.

The biochemical structure and functional significance of the Cromer blood group came to light when it was shown that these antigens are carried on a protein known as "decay accelerating factor" (DAF). The DAF protein was well known to scientists studying complement, ie. a group of proteins important in inflammation. DAF is a regulatory protein which controls several of the complement components known as the C3 convertase. Today, all of the different Cromer/DAF genes have been cloned and the exact mutations identified. Cr^a is due to a G-C change in SCR4 leading to an ala193pro substitution. Most of the other Cromer system antigens have been found in SCR1 at the DAF protein.

Individuals who acquire a deficiency of DAF on their red blood cells develop an anemia known as paroxysmal nocturnal hemoglobinuria (PNH). However, extremely rare individuals have an inherited form of DAF deficiency. This is know as the "Inab" phenotype and these red cells lack all of the Cromer blood group antigens as well as the DAF protein. Interestingly, the Dr^a antigens carried on DAF play a unique role in the binding of a bacteria, ie. Escherichia coli, to the lining of the urinary tract. It appears that the bacteria uses the DAF protein for attachment to the cell lining in order to establish infection.