In order to establish the role of fetomaternal ABO incompatibility as a cause of overall neonatal jaundice, its relationship to the degree of jaundice, and its etiologic contribution to severe jaundice necessitating exchange transfusion in South African blacks, a retrospective analysis of both laboratory and clinical data was undertaken. Two thousand forty-two blood samples were submitted for laboratory investigation from mothers and their jaundiced newborn infants and categorized according to ABO blood groups and levels of serum bilirubin. At levels of serum bilirubin below 301 mumol/l, ABO incompatible combinations occurred as frequently as ABO compatible combinations. However, at serum bilirubins above 301 mumol/l, ABO incompatibility was a major cause of jaundice in almost 58 per cent of infants. In the nursery-based clinical studies, ABO incompatibility accounted for 41.7 per cent of those severely jaundiced (greater than 301 mumol/l) and 44.4 per cent of newborn infants who had exchange transfusions. ABO incompatible combinations however did not assume a significant role in the cause of overall neonatal jaundice. Both laboratory and clinical findings therefore confirm the importance of fetomaternal ABO incompatibility as a cause of severe jaundice and an unimportant cause of overall jaundice in newborn black babies.