Background. To evaluate if dissolution of asparaginase in lidocaine can relieve pain of an intramuscular injection in children without changes in bioavailability. Procedure. The study was designed as a double-blinded study, randomizing 12 children with acute lymphoblastic leukemia (ALL) to four different combinations of injections, including two injections where asparaginase was dissolved in a lidocaine solution and two in sterile water. Seventeen treatment courses of asparaginase, each consisting of four injections, were evaluated. Pain intensity (Pain Visual Analog Scale, VAS-score) and pharmacokinetics of the drug was evaluated. Results. The pain scores showed a significant difference between the two solutions of asparaginase (+/-\idocaine) (P value < 0.0001). Lidocaine did not influence the pharmacokinetics of the drug. Conclusions. Asparaginase with addition of lidocaine significantly decreases the pain as measured by the visual analog scale without changing the bioavailability or the absorption rate of the enzyme. (C) 2004 Wiley-Liss, Inc.