The Rh blood group system is one of the most polymorphic and immunogenic systems known at this time in humans. It is controlled by two genes, that encode two distinct Rh proteins. One protein carries the C/c and E/e antigens, and is therefore called the Rh CE or Rh ce (or Rh Ce or Rh cE) protein. The other carries the Rh D antigen, and is called Rh D protein. A fourth Rh antigen, Rh G, is located partly on the Rh CE and partly on the Rh D protein.

The genes encoding these two proteins have been cloned, end the molecular basis of the immunogenicity is being studied extensively world wide.

Rh D is a protein that sits in the plasma membrane of red blood cells. It crosses the membrane 12 times, creating 6 extracellular loops, and 5 intra cellular loops. Both the carboxy- and the amino-tail of the protein stick out into the interior of the cell.

The presence or absence of the Rh D protein from red blood cells determines if one is typed Rh+ (protein is present) or Rh- (protein is absent).

The Rh D blood group system is the second most immunogenic system known at this time. Only the ABO system has greater clinical importance.