Leukemia in the first year of life is extremely rare world-wide. However, unlike leukemias in older children, nearly 75% of infant leukemias demonstrate a specific abnormality involving a gene, MLL, on chromosome band 11q23. Molecular studies suggest strongly that these leukemias occur in utero. Treatment-related acute myeloid leukemias (AML), associated with specific chemotherapeutic agents that inhibit DNA topoisomerase II (topo 2), also manifest identical abnormalities involving the MLL gene. This led us to speculate that maternal exposure during pregnancy to environmental agents that inhibit DNA topo 2 may be associated with the development of leukemia in infants. DNA topo 2 inhibitors have been found in specific fruits and vegetables, and in soy, coffee, wine, tea and cocoa, as well as in certain pesticides, solvents and medications. In a preliminary study, we reinterviewed mothers of infant cases and their matched controls who had participated previously in 1 of 3 epidemiologic studies of childhood leukemia conducted by the Children's Cancer Group over a 10-year period. We evaluated potential DNA topo 2 inhibitor exposure through maternal diet and medications. Of the 84 original matched sets who were reinterviewed, there was no positive association with increasing maternal consumption of DNA topo 2 inhibitor-containing foods either for the overall group or for infants in the acute lymphoblastic leukemia stratum. However, there was an approximately 10-fold higher risk of infant AML with increasing maternal consumption of DNA topo 2 inhibitor-containing foods. The assay to screen environmental agents that inhibit DNA topo 2 has been established and new inhibitors are being identified routinely.