Inter-individual differences in cancer susceptibility may be mediated in part through polymorphic variability in the bioactivation and detoxification of carcinogens. The glutathione S-transferases (GSTs), which are active in detoxification of wide variety of carcinogens, have been consistently implicated as cancer susceptibility genes in this context. We here assessed the association of GSTM1 and GSTP1 polymorphisms with susceptibility to prostate cancer in a case-control study of 75 patients and 100 age-matched controls in a South Indian population. The GSTM1 null polymorphism was detected by PCR and the GSTP1 Ile105Val polymorphism by PCR-RFLP using peripheral blood DNA. There was no significant link between the null genotype of GSTM1 and risk of prostate cancer (OR-1.79; 95% CI-0.78-4.11; P-0.18). However, the GSTP1 Ile/Val genotype was significantly associated with a decreased risk for prostate cancer (OR-0.36; 95% CI-0.18-0.73; P<0.001). Analysis of the variant GSTM1 and GSTP1 genotypes in combination did not reveal any significant difference between cases and controls, even with a stratified analysis tumor grades. Thus our study indicates that the GSTP1 Ile/Val genotype may decrease risk of prostate cancer in the South Indian population.