Oxidative polymorphism of debrisoquine (DBQ) was determined in 98 women with breast cancer (mean age 59.2 years, SD 10.7; 18 were premenopausal when diagnosed), and in 446 healthy control women (mean age 25.4 years, SD 9.15). All of them were free of drug interactions with oxidation of DBQ. Ten patients (10.2%), all of them postmenopausal when diagnosed, and 423 controls (5.2%), with values for metabolic ratio of DBQ greater than 12.6, were classified as poor metabolizers (PM) of DBQ (p = 0.006). Relative risk for developing breast cancer among women with PM phenotype was 2.09 (95% confidence limits 0.97-4.48). The PM status of DBQ might be a secondary risk factor for breast cancer in postmenopausal women.