Anti-D isoimmunisation remains the most common cause of erythroblastosis fetalis. Whereas most clinically significant blood group sensitisations noted during pregnancy are still secondary to anti-D incompatibility, sensitisation to antigens other than D in the CDE system is not uncommon and can cause severe disease. The widespread use of Rh-D immune globulin has led to a relative increase in the importance of non-Rh-D isoimmunisation as a cause of haemolytic disease of the newborn. We report the case of a baby with severe hyperbilirubinaemia and persistent anaemia due to anti-c isoimmunisation with a high-titre maternal c antibody. The baby required emergency transfusion and intensive phototherapy. The medical literature relating to maternal c isoimmunisation and neonatal outcome is also reviewed. Because of its ability to cause clinically significant haemolytic disease of the newborn, practitioners must manage anti-c isoimmunisation in a manner similar to that for anti-D.