Rhesus is the clinically most important protein-based blood group system. It represents the largest number of antigens and the most complex genetics of the 30 known blood group systems. The RHD and RHCE genes are strongly homologous. Some genetic complexity is explained by their close chromosomal proximity and unusual orientation, with their tail ends facing each other. The antigens are expressed by the RhD and the RhCE proteins. Rhesus exemplifies the correlation of genotype and phenotype, facilitating the understanding of general genetic mechanisms. For clinical purposes, genetic diagnostics of Rhesus antigens will improve the cost-effective development of transfusion medicine.

Patients carrying any of the prevalent weak D types 1, 2, 3 or 4.1 are not prone to allo-anti-D immunization and may safely be transfused with D-positive red blood cells. Pregnant women with these weak D types need not receive RhIg. We should pay attention to weak D- or DEL-positive blood units that are labelled D-negative. The clinical benefit of removing DEL blood units from our supply of D-negative red blood cell units should be determined.