Genes that metabolize the rate of clearance of environmental carcinogens may be candidate genes for cancer susceptibility. There is some data to suggest that exposure to environmental pesticides and other organochlorine pollutants is a risk factor to breast cancer. It is therefore reasonable to ask if variants in the genes responsible for the metabolic activation of organochlorines are associated with different tissue burdens of organochlorines and if these variants modify the risk of breast cancer in the population. We conducted a case-control study of women who underwent an excision biopsy for suspected breast cancer in a Toronto hospital from 1995 to 1997. Patients are residents of the Greater Toronto Area and are primarily Caucasian of European descent. Cases were women with invasive breast cancer (n = 70) and controls (n = 69) were women diagnosed with benign disease, frequency matched by age to cases. Levels of organochlorines were measured in benign breast tissue and seven polymorphisms in five candidate genes were genotyped. In general, women who carried inactive alleles of the GSTM1 had higher levels of breast organochlorines, and were at modestly increased risk of breast cancer (odds ratio = 2.2; 95% CI = 1.1-4.4). However, multiple comparisons were made and generally our data do not support the hypothesis that organochlorines increase the risk of breast cancer among subgroups of women with specific metabolic genotypes.