The potential interaction of GSTM1 and GSTP1 genotypes in pulmonary carcinogenesis was assessed in 382 male Japanese lung cancer patients (127 squamous cell carcinoma, 78 small cell carcinoma, 177 adenocarcinoma) and 257 controls. In smokers (358 cases, 184 controls) the GSTM1 null genotype was more distributed in individuals with at least one GSTP1 mutant allele compared to those without, in lung cancer patients (69.5% vs.53.2%) but not in controls (48.0% vs. 48.5%). No such relationship was detected in non-smokers (24 cases, 73 controls). The estimated relative risk of the GSTM1 null genotype for lung cancer was 2.58 (95%CI = 1.26-5.30) in smokers with the GSTP1 mutant allele while it was 1.17 (95%CI = 0.77-1.79) in those without, suggesting that mutated GSTM1 and GSTP1 genotypes interact to potentiate the risk of lung cancers in Japanese smokers.