Objective: This study was undertaken to evaluate the impact of hormone replacement therapy on results of quantitative ultrasonometry of the heel. Study Design: A total of 2006 healthy perimenopausal women (mean age, 52.2 (10.3 years) were recruited in 5 German centers: 611 women (30%) had received hormone replacement therapy and 1395 (70%) had not. About 90% of the hormone replacement therapy users were current users, and the rest had stopped <6 months before the study. Speed of sound, broadband ultrasonographic attenuation, and the stiffness index were compared among the following groups: all users and nonusers of hormone replacement therapy, hormone replacement therapy users and nonuser control subjects matched for age and body mass index, and hormone replacement therapy users grouped in relation to the duration of hormone replacement therapy use and age and control subjects matched for body mass index. Results: Women who were using hormone replacement therapy had significantly higher values (P <.001) than did nonusers for all ultrasonographic variables, even after we controlled for age and body mass index. Women who had used hormone replacement therapy for >3 years had significantly higher values (P <.001) than did matched control subjects for all variables. Differences increased with the duration of hormone replacement therapy use. Conclusion: Quantitative ultrasonometric measurement at the heel differentiates hormone replacement therapy users from nonusers, reflects duration of hormone replacement therapy use, and could be useful in both clinical trials and patient management. (Am J Obstet Gynecol 2000;182:529-34.)