Background: The management of hyperleukocytosis currently involves intensive supportive care for preventing tumor lysis syndrome (TLS)-associated metabolic abnormalities as well as cytoreduction procedures to reduce the white blood cell (WBC) count. These procedures are often equipment-intensive and may not be practised in developing countries with limited resources. Hence, it is not clear what would be the most effective strategy to manage hyperleukocytosis and prevent TLS. Procedure: All children ≤12 years, diagnosed with acute lymphoblastic leukemia (ALL) and hyperleukocytosis (WBC count >100 × 10<sup>9</sup>/l) were administered <smlcap>L</smlcap>-asparginase (<smlcap>L</smlcap>-asp, 6,000 U/m<sup>2</sup>, i.m.) along with standard supportive care consisting of hydration, oral allopurinol administration and alkalization. The complete blood counts and biochemical parameters were monitored for 72 h. After 48 h, if the WBC count was >100 × 10<sup>9</sup>/l, a repeat dose of <smlcap>L</smlcap>-asp was administered. Results: Twenty-one children (9 boys and 12 girls) with hyperleukocytic ALL were treated with <smlcap>L</smlcap>-asp. The median age of the children was 5.3 years (range 2-11 years). The median initial WBC count was 249 × 10<sup>9</sup>/l (range 151-476 × 10<sup>9</sup>/l). Twenty children received only one dose of <smlcap>L</smlcap>-asp. The mean reduction in WBC count achieved by treatment was 15.7, 42.0, 61.0, 76.4, 85.5 and 90.8% at 12, 24, 36, 48, 60 and 72 h, respectively. None of the patients developed TLS. Conclusions: Chemical cytoreduction by administering <smlcap>L</smlcap>-asp is an effective means of managing hyperleukocytosis and preventing TLS.