The enzyme L-asparaginase is a crucial component in the treatment of acute lymphoblastic leukemia (ALL). As all asparaginases in clinical use are derived from microorganisms, immunological reactions are the most important adverse events associated with asparaginase treatment. Two different methods, phage display and the SPOTs method, were used for the determination of clinically relevant epitopes. Comparison of the results showed that essentially the same domains were identified by the two methods, and thus ascertainment of relevant epitopes can be assumed. Determination of the specificity of the epitopes will be performed with serum from patients with different modes of immunological reactions and from individuals without evidence of an immune response after asparaginase administration.