OBJECTIVE: To study the relationship between glutathione S-transferase genes GSTT1 and GSTM1 polymorphisms and the susceptibility to infectious mononucleosis (IM) and acute lymphocytic leukemia (ALL) in children. METHODS: The case-control study involved 106 children with IM, 41 children with ALL and a control group of 100 children with non-hematologic and nontumorous diseases. The genetic polymorphisms of GSTT1 and GSTM1 were detected with multiplex polymerase chain reaction (PCR). Distribution of the genotypes in the children was analyzed. RESULTS: The frequency of GSTT1 null genotype in children with IM was significantly higher than in the control group (P<0.05). The risk of IM in children carrying GSTT1 null genotype was 2.186 times higher than in those carrying GSTT1 non-null genotype. The children carrying both GSTT1 and GSTM1 null genotype had a higher risk of suffering from IM compared to those carrying only one of the null genotypes (OR=4.937). The frequency of GSTM1 null genotype in children with ALL was significantly higher than in the control group (P<0.05). The risk of ALL in children carrying GSTM1 null genotype was 2.242 times higher than in those in carrying GSTT1 non-null genotype. Children carrying both GSTT1 and GSTM1 null genotype had a higher risk of suffering from ALL compared with those carrying only one of the null genotypes (OR=8.552). CONCLUSIONS: Children carrying GSTT1 or GSTM1 null genotype have a high risk of suffering from IM or ALL. Still more increased susceptibility to IM or ALL may occur in children who carry both GSTT1 and GSTM1 null genotype. GSTT1 and GSTM1 might play a potential role in the pathogenesis of both IM and ALL.