Infection with Opisthorchis viverrini (OV) is associated with cholangiocarcinoma. OV is common in northeast Thailand, but less than 10% of the inhabitants develop cholangiocarcinoma. Animal experiments suggest that OV infection alone does not cause cholangiocarcinoma, and thus other environmental and genetic factors may play a role in causation. We conducted a population-based case-control study in which sex, age and place of residence were matched individually. Polymorphisms of GSTM1 and GSTT1 alone were not associated with risk for cholangiocarcinoma, while an elevated level of antibodies against OV (ELISA) ≥0.200 was the strongest risk indicator (odds ratio as compared to that <0.200 = 27.09 [95% confidence interval (CI): 6.30–116.57]. Compared to subjects who had a normal antibody range and the wild-type GSTM1 gene, those who had elevated antibodies had higher odds ratios of 12.32 (95% CI: 1.60–94.85) for wild-type GSTM1 and 23.53 (95% CI: 4.25–130.31) for the null variant thereof, respectively. Past and current regular drinkers of alcohol had higher risk [odds ratio = 5.39 (95% CI: 1.11–26.06) and 4.82 (95% CI: 1.29–18.06), respectively]. Eating fermented products was an independent risk factor. Smokers or consumers of fermented fish had substantially increased risk if they were past or current drinkers. Infection with OV correlates strongly with cholangiocarcinoma, susceptibility to which may be possibly associated with GSTM1 polymorphism. Alcohol may affect metabolic pathways of endogenous and exogenous nitrosamines. © 2005 Wiley-Liss, Inc.