The polymorphic enzyme alcohol dehydrogenase (ADH) catalyses the conversion of ethanol into the carcinogenic metabolite acetaldehyde which is partly excreted into the urine. Objectives of this pilot study are to determine whether this polymorphism may be related to bladder cancer and whether it modifies the relation between alcohol intake and bladder cancer. 120 bladder cancer patients and 133 convenience controls were recruited at the University Medical Centre Nijmegen. A self-administered questionnaire was used to assess alcohol intake and potential confounders. DNA was isolated from peripheral blood, and ADH3 genotype was determined using PCR/RFLP. People with the ADH3 genotype gamma1gamma1 were compared to people with other ADH3 genotypes. Above moderate drinkers (>14 glasses of alcohol per week) were compared to moderate drinkers. Odds ratios (ORs) and 95% confidence intervals were computed using logistic regression analyses. After correction for sex, age and smoking, ORs for ADH3 genotype and alcohol intake were 2.10 (1.05-4.22) and 1.21 (0.60-2.44), respectively. Moderate drinkers with the 'high-risk' (gamma1gamma1) ADH3 genotype appeared to have a threefold higher risk of bladder cancer compared to moderate drinkers with a 'low-risk' (gamma1gamma2 or gamma2gamma2) genotype. Surprisingly, the ORs for above moderate drinkers with the low-risk genotype (1.95; 95% CI: 0.85-4.48) and with the high-risk genotype (2.18; 95% CI: 0.82-5.77) were almost similar, suggesting no interaction. ADH3 genotype is a possible risk factor for bladder cancer. Although moderate drinkers with the gamma1gamma1 genotype seem to have the highest risk, we did not get a clear indication that ADH3 genotype modifies the relationship between alcohol intake and bladder cancer.