Suspected nephrocarcinogenic effects of trichloroethene (TRI) in humans are attributed to metabolites derived from the glutathione transferase (GST) pathway. The influence of polymorphisms of GSTM1 and GSTT1 isoenzymes on the risk of renal cell cancer in subjects having been exposed to high levels of TRI over many years was investigated. GSTM1 and GSTT1 genotypes were determined by internal standard controlled polymerase chain reaction. Fourty-five cases with histologically verified renal cell cancer and a history of long-term occupational exposure to high concentrations of TRI were studied. A reference group consisted of 48 workers from the same geographical region with similar histories of occupational exposures to TRI but not suffering from any cancer. Among the 45 renal cell cancer patients, 27 carried at least one functional GSTM1 gene (GSTT1 +) and 18 at least one functional GSTT1 gene (GSTT1 +). Among the 48 reference workers, 17 were GSTM1 + and 31 were GSTT1 +. Odds ratio for renal cell cancer were 2.7 for GSTM1 + individuals (95% CI, 1.18-6.33; P < 0.02) and 4.2 for GSTT1 + individuals (95% CI, 1.16-14.91; P < 0.05), respectively. The data support the present concept of the nephrocarcinogenicity of TRI.