The interplay between genetic susceptibility and exposure to carcinogens has been shown to be involved in the etiology of many solid tumors. We studied the frequency and clinical correlates of polymorphisms resulting in deletions of two genes involved in the detoxification of potentially carcinogenic agents, glutathione S-transferase (GST)-M1 and GSTT1 in patients with Hodgkin's lymphoma (HL).The prevalence of gene deletions in 90 patients with HL was compared with a case-matched cohort of 176 normal blood donors. GST gene polymorphisms were studied using a multiplex PCR method, including the BCL2 gene as an internal control.Deletions of the GSTT1 gene were more frequent in cases compared with controls (28.9 versus 17.6%, P = 0.04), resulting in an increased risk for HL in individuals with the GSTT1-null genotype (odds risk, 1.9; 95% confidence interval 1.04-3.46). The GSTT1-null genotype particularly increased the HL risk in females aged <45 years (odds risk 6.1, 95% confidence interval 1.6-23, P = 0.008). Correlating patient characteristics to genotype, we found an association between the GSTT1-null genotype and a limited stage of disease (I/IIA versus IIB-IV, 40.6 versus 19.6%, P = 0.047) and an erythrocyte sedimentation rate of <50 mm/h (P = 0.02). Patients with at least one GST deletion (GSTM1- or GSTT1-) had a significant better disease-free survival when compared with those with undeleted GST genes (GSTM1+/GSTT1+; P = 0.012).The GSTT1-null genotype may increase the risk for HL and is associated with favorable prognostic factors, and the presence of at least one GST deletion indicates an improved disease-free survival.