The increased incidence of leukemia in patients with trisomy 21 is well established. A blood disorder which may be mistaken for acute leukemia may occur in infants with trisomy 21. The authors report a newborn with trisomy 21 and hematologic findings suggesting acute leukemia (hyperleukocytosis, anemia, thrombocytopenia; replacement of bone marrow by blast-like cells). Without treatment spontaneous and complete recovery occurred. Cytochemistry and therapy are discussed in this paper.