Postmenopausal women with increased estrogens and lowered sex hormone-binding globulin (SHBG) concentrations are at increased risk of breast cancer. In the Multiethnic Cohort Study, the highest incidence rates of postmenopausal breast cancer were observed among Native Hawaiians followed by Japanese Americans, Whites, African Americans, and Latinas. Ethnic differences in endogenous sex hormone profiles may contribute to some of the variation in breast cancer incidence. Plasma concentrations of androstenedione, testosterone, estrone (E(1)), estradiol (E(2)), and SHBG were measured in 739 postmenopausal women from the Multiethnic Cohort Study (240 African Americans, 81 Native Hawaiians, 96 Japanese Americans, 231 Latinas, and 91 Whites). After adjusting for age, known breast cancer risk factors and lifestyle factors, the mean levels of testosterone, estrogen, and SHBG varied across populations (Ps < or = 0.004). Across racial/ethnic groups, Native Hawaiians had the highest mean levels of androstenedione, testosterone, and estrogens and the lowest mean levels of SHBG. Compared with Whites, Native Hawaiians had higher androstenedione (+22%, P = 0.017), total testosterone (+26%, P = 0.013), bioavailable testosterone (+33%, P = 0.002), E(1) (> or =21%; P = 0.009), total E(2) (+26%, P = 0.001), bioavailable E(2) (+31%, P < 0.001), and lower SHBG (-12% P = 0.07) levels. Compared with Whites, Japanese Americans had higher E(2) (+15%, P = 0.036) and bioavailable E(2) (+18%, P = 0.024) levels. African Americans also had higher E(1) (+21%, P = 0.004), E(2) (+20%, P = 0.007), and bioavailable E(2) (+20%, P = 0.015) levels compared with Whites, whereas mean levels in Latinas were similar to those of Whites. Many of the differences in endogenous postmenopausal hormonal milieu across these five racial/ethnic groups are consistent with the known differences in breast cancer incidence across these populations.