Two normal appearing infants presented in the newborn period with elevated white blood cell counts and immature blast cells. Initial bone marrow karyotype analysis showed trisomy of chromosome 21 in all metaphases. In both patients blastemia spontaneously resolved and percentage of trisomy 21 cells decreased. One infant required multiple exchange transfusions and pericardiotomy. The other patient had undifferentiated blasts and continued to have subtle hematopoietic abnormalities greater than 2 years later. Both children have had normal growth and development. The clinical course of these patients emphasizes the need for aggressive supportive care without use of cytotoxic drugs in phenotypically normal newborns with blastemia showing trisomy 21.