We determined retrospectively the frequency and risk of hyperglycemia in 421 children with leukemia who had received l-asparaginase and prednisone as part of their remission induction therapy. Forty-one patients (9.7%) developed this complication, 39 within one week after the first dose of l-asparaginase. Hyperglycemia resolved in all patients and in 32 before the end of the four-week induction period. Age, obesity, and Down syndrome each had a significant bearing on the frequency of hyperglycemia. Children 10 years of age or older were more likely to develop the complication than were younger children. When more than one factor was present in a child, the risk of hyperglycemia increased significantly. A family history of diabetes mellitus also appeared related to an increased risk of hyperglycemia. Childhood leukemia patients with any of the risk factors identified here should be closely monitored for glucosuria while receiving prednisone and l-asparaginase for remission induction.