The cross-sectional relationship between long-term estrogen use and vertebral (L2-4) bone mineral density (BMD) was determined in 65 postmenopausal white women between 55 and 75 years who were at least 10 years from their menopause. Long-term estrogen users began therapy within 5 years of menopause and continued for a duration of at least 10 years. The mean duration of use was 19.8 years. Controls used estrogen for less than 1 year. There was a significant difference (p less than 0.02) in mean spinal BMD between estrogen users (1.219 g/cm2) and controls (1.092 g/cm2). There was no significant difference in age, height, weight, or dietary calcium (Ca) intake between the two groups. The statistical difference in BMD was retained when (1) 23 estrogen users were paired with age-matched controls, (2) only women with a natural menopause or history of bilateral oophorectomy were included, and (3) only women with a natural menopause were compared. A spinal BMD below the estimated fracture threshold of 0.965 g/cm2 was found in 11 of 40 controls and only 2 of 25 estrogen users. Comparison of estrogen users with a natural menopause to those with bilateral oophorectomy revealed no significant difference in BMD. These data confirm the salutary effect of long-term estrogen use in the maintenance of vertebral bone mass in postmenopausal women.