The environmental organochlorines 2,2-bis(p-chlorophenyl)1,1,1,trichloroethane (DDT) and polychlorinated biphenyls (PCBs) have been implicated as potential causes of female breast cancer. We continued follow-up of our 1997 case-control study nested in the Nurses' Health Study cohort, adding 143 postmenopausal cases and controls to the original 238 pairs, and examining specific PCB congeners for the first time. We measured plasma levels of 2,2-bis(p-chlorophenyl)ethylene (DDE), the major metabolite of DDT, and PCBs prospectively, comparing women who were diagnosed with breast cancer between 1 month and 4 years after blood collection with control women in whom breast cancer did not develop. Median concentrations of lipid-adjusted DDE, total PCBs, and PCB numbers 118, 138, 153 and 180, assessed individually, were similar among the cases and controls. The multivariate relative risk of breast cancer for women in the highest quintile of exposure as compared with women in the lowest quintile was 0.82 for DDE (95% confidence interval [CI]: 0.49–1.37) and 0.84 for total PCBs (95% CI: 0.47–1.52), 0.69 for PCB 118 (95% CI: 0.39–1.22), 0.87 for PCB 138 (95% CI: 0.50–1.50), 0.83 for PCB 153 (95% CI: 0.47–1.48), and 0.98 for PCB 180 (95% CI: 0.55–1.75). Sub-group analyses were also performed. Overall, our results do not support the hypothesis that exposure to DDT and PCBs increases the risk of breast cancer. © 2001 Wiley-Liss, Inc.