The oxidative polymorphism of debrisoquine has been determined in 125 patients with bladder cancer and in 556 healthy control subjects; 96.6% of patients and 93.9% of controls with a metabolic ratio of debrisoquine less than 12.6 were classified as extensive metabolizers of debrisoquine (P = NS). The distribution of frequencies of metabolic ratio values tended to have lower values in the patients (P less than 0.05), reflecting a higher oxidative rate of debrisoquine in urothelioma patients that cannot be explained solely in terms of enzymatic induction by drugs, tobacco or alcohol. Patients with a high occupational risk for urothelioma had lower metabolic ratio values (P = 0.03). Our results suggest that oxidative polymorphism of debrisoquine might be related to the pathogenesis of bladder cancer.