Caffeine intake has been associated with risk of osteoporosis, breast cancer, endometriosis, and fibrocystic breast disease and has been hypothesized to exert its effects through alteration of endogenous hormone levels. This study examined the cross-sectional association of caffeine intake with endogenous androgens, estrogens, and sex hormone-binding globulin in 728 white postmenopausal women aged 42-90 years in the Rancho Bernardo community-based study in 1984-1987. Caffeine intake was inversely associated with age and waist/hip ratio and positively associated with alcohol consumption. Significant inverse associations were noted between caffeine intake and bioavailable testosterone, which persisted after adjustment for age, waist/hip ratio, body mass index, alcohol intake, cigarette smoking, and physical activity (r = -0.10, p = 0.02). At high doses (equivalent to more than 2 cups of coffee or four cans of caffeinated soda daily), caffeine intake was positively associated with plasma estrone before and after adjustment for confounders (r = 0.26, p = 0.05). Sex hormone-binding globulin levels were positively associated with increasing caffeine intake (adjusted r = 0.09, p = 0.03). The positive association of caffeine with estrone and its inverse association with bioavailable testosterone suggest that caffeine's reported association with several chronic conditions may be mediated by an effect on endogenous sex steroids.