Environmental exposure to organochlorine compounds has been associated with a potential role in breast cancer etiology, but results from previous investigations yielded inconsistent results. In this case-control study, we examined the effect of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), hexachlorobenzene (HCB), mirex, and several measures of polychlorinated biphenyls (PCBs) on postmenopausal breast cancer risk. The study sample included 154 primary, incident, histologically confirmed, postmenopausal breast cancer cases and 192 postmenopausal community controls. Usual diet, reproductive and medical histories, and other lifestyle information was obtained by an extensive in person interview. Serum levels (ng/g) of DDE, HCB, mirex, and 73 PCB congeners were determined by gas chromatography with electron capture. PCB exposure was examined as total measured PCB levels, total number of detected PCB peaks, and three PCB congener groups. In the total sample, there was no evidence of an adverse effect of serum levels of DDE [odds ratio (OR), 1.34; 95% confidence interval (CI) 0.71-2.55], HCB (OR, 0.81; 95% CI, 0.43-1.53), or mirex (OR, 1.37; 95% CI, 0.78-2.39). Further, higher serum levels of total PCBs (OR, 1.14; 95% CI, 0.61-2.15), moderately chlorinated PCBs (OR, 1.37; 95% CI, 0.73-2.59), more highly chlorinated PCBs (OR, 1.19; 95% CI, 0.60-2.36), or greater number of detected peaks (OR, 1.34; 95% CI, 0.72-2.47) were not associated with increased risk. There was some indication of a modest increase in risk for women with detectable levels of less chlorinated PCBs (OR, 1.66; 95% CI, 1.07-2.88). Among parous women who had never lactated, there was some evidence for increased risk, associated with having detectable levels of mirex (OR, 2.42; 95% CI, 0.98-4.32), higher serum concentrations of total PCBs (OR, 2.87; 95% CI, 1.01-7.29), moderately chlorinated PCBs (OR, 3.57; 95% CI, 1.10-8.60), and greater numbers of detected PCB congeners (OR, 3.31; 95% CI, 1.04-11.3). These results suggest that an increase in risk of postmenopausal breast cancer associated with environmental exposure to PCBs and mirex, if at all present, is restricted to parous women who had never breast-fed an infant. Future studies should consider lactation history of participants, as well as use similar epidemiological and laboratory methodologies, to ensure comparability of results across studies.