In children with acute lymphoblastic leukaemia (ALL) treated according to protocols of the Berlin-Frankfurt-Münster (BFM) study group, the initial response to prednisone is the strongest predictor of therapy outcome. Glutathione S-transferases (GSTs) have been implicated in glucocorticoid resistance. In order to assess a potential association of phenotypically relevant GST polymorphisms with prednisone response in childhood ALL, we conducted a case–control study of 45 prednisone poor-responders (cases) and 90 prednisone good-responders (controls) who were frequency matched according to initial white blood cell count. In addition, we analysed the association of GST genotypes with relapse of leukaemia. In univariate analysis, homozygous deletion ofGSTT1(null genotype) conferred a 6.7-fold reduction in risk of prednisone poor-response compared to individuals who were either heterozygous or homozygous forGSTT1[odds ratio (OR) = 0.15,P= 0.071; multivariate odds ratio = 0.18,P= 0.117].GSTM1andGSTP1genotypes did not show any association with prednisone response. In addition, risk of relapse was predicted strongest by theGSTT1genotype. In univariate analysis, theGSTT1null genotype conferred a 5.9-fold reduction in risk of relapse compared to the heterozygous or homozygous presence ofGSTT1(OR = 0.17,P= 0.095; multivariate OR = 0.23;P= 0.173). No associations of theGSTM1genotype with risk of relapse were observed.GSTP1codon 105 and codon 114 polymorphisms were predominantely associated with central nervous system relapse. Our results add further support to the hypothesis that genetic polymorphisms within specific GST genes might be of clinical importance in childhood ALL.