Antioxidants may protect against free radical mediated carcinogenesis. Epidemiological studies have not confirmed this hypothesis for breast cancer, possibly because of methodological limitations. Time-integrated exposure of alpha-tocopherol and beta-carotene in adipose tissue, and selenium in toenails was investigated in a case-control study among postmenopausal women, ages 50-74 years, from five European countries. The study group comprised 347 incident breast cancer cases and 374 controls. Mean antioxidant levels, adjusted for age and center, did not significantly differ for alpha-tocopherol (cases were 4.5% higher than controls), beta-carotene (3.0% lower), or selenium (1.8% lower). Odds ratios for highest versus lowest tertiles of exposure, adjusted for potential confounders, were 1.15 (95% confidence interval, 0.75-1.77), 0.74 (0.45-1.23), and 0.96 (0.63-1.47), respectively, without evidence for a decreasing trend. No statistically significant interactions were observed. Moreover, a provisional antioxidant score, indicating whether concentrations were above the median for zero, one, two, or all three antioxidants, yielded odds ratios of 1.00 (reference; all below median), 1.58, 1.58, and 1.21, respectively (chi2 for association = 4.00; P = 0.26). These results do not support the hypothesis that antioxidants are important determinants of this hormone-related malignancy among postmenopausal women.