A blood requisition for double-volume exchange transfusion was received for a 2-day-old male child born to a 29-year-old multiparous female (P2002) referred to our institute having neonatal jaundice with encephalopathy; no maternal sample was received. the neonatal blood sample was typed as group A, D-, and the direct antiglobulin test (DAT) was strongly positive (4+) using the gel method. Mono-specific DAT showed the presence of IgG antibodies on neonatal red blood cells (RBCs). Acid elution and gentle heat elution (at 56°C) confirmed the presence of anti-D on neonatal RBCs. The baby received two exchange transfusions with group O, D-, packed RBCs compatible with his own serum. Later, on day 3, the neonate's mother was typed as group AB, D-, and her serum revealed the presence of alloanti-D, -C, and -S reactive in the anti-human globulin phase. The anti-D titer was 1024. this report highlights the "blocking" phenomenon caused by maternal anti-D in a case of hemolytic disease of fetus and newborn with a positive DAT.