A monoclonal antibody (MoAB) has been developed which reacts with a previously unidentified hematopoietic cell surface protein called MKW. This MoAB (anti-MKW) does not cluster with antibodies in any of the known cluster groups of differentiation. Blast cell expression of MKW was studied in 196 consecutively diagnosed children with acute lymphoblastic leukemia (ALL), 69 children with previously untreated acute myeloblastic leukemia (AML) and four children with secondary AML. MKW expression, clinical, laboratory and cytogenetic features at diagnosis, and treatment response and duration were examined for significant correlations. MKW was expressed on blasts from 12.8% of children with ALL and 24.6% of children with de novo AML. The expression of MKW appears to be more common in patients with secondary AML (three of four) than de novo AML (17 of 69). In patients with AML, the expression of MKW was correlated with an elevated initial leukocyte count (p = 0.0005) and poorer disease-free survival (p = 0.04). In patients with ALL, the expression of MKW was associated with a lower hemoglobin level (p less than 0.05) and a lower complete remission rate (p = 0.02). At a median follow-up of 4.6 years ALL patients with greater than or equal to 50% MKW+ blasts had a poorer event-free survival (EFS) than both MKW+ patients with 25-49% positive blasts (p = 0.03) and MKW+ patients (p = 0.0001). The disease-free survival was also poorer for ALL patients with greater than or equal to 50% MKW+ blasts (p = 0.02). In Cox regression analysis, the expression of MKW had an independent prognostic significance in children with ALL. As MKW is a unique cell surface antigen and its expression has prognostic significance in acute leukemias in children, further study in a larger series of patients is warranted.