Plasma levels of alpha- and beta-isomers of cholesterol-5, 6-epoxides were quantitated in a pilot study of 9 women with endometrial cancer and 9 race- and age-matched control women by isotope dilution gas chromatography/mass spectrometry. Endometrial cancer cases had significantly higher cholesterol-5 beta,6 beta-epoxide levels than the controls (P = 0.01). The mean plasma beta-epoxide level was 0.71 +/- 0.46 ng/ml for the cases and 0.35 +/- 0.25 ng/ml for the controls. No significant differences were found between the plasma alpha-epoxide levels of the cases and the controls. Plasma levels of various carotenoids, tocopherols, and ascorbic acid were also quantitated by high performance liquid chromatography. An inverse correlation was present between the plasma levels of cholesterol-5 beta,6 beta-epoxide and cis-lutein/zeaxanthin (P = 0.01). These data suggest a possible role for cholesterol-5 beta,6 beta-epoxide as a biomarker of endometrial cancer risk. Further studies are warranted to investigate the possible association between the oxidation products of cholesterol and endometrial cancer and to determine the interactive role of antioxidants.