We determined the site-specific relations of hormone replacement therapy (HRT) and habitual exercise status with intima-media thickness (IMT) in both elastic (carotid) and muscular (femoral) arteries in 77 healthy postmenopausal women: 43 women were sedentary (20 no-HRT and 23 HRT users) and 34 women were endurance trained (14 no-HRT and 20 HRT users). Femoral IMT was not different among the sedentary HRT and endurance-trained no-HRT and HRT groups, but was lower (P < 0.005) in these three groups than in the sedentary no-HRT women. There were no significant group differences in carotid IMT. However, in older women (> or =65 yrs) carotid IMT was smaller (P < 0.05) in HRT compared with no-HRT women. We conclude that both endurance training and HRT status are independently associated with a smaller IMT and these effects are evident primarily in muscular arteries. These results suggest that HRT and habitual exercise may protect postmenopausal women against cardiovascular disease through influences on IMT. The site-specific relations may be due to a greater number of smooth muscle cells and plasticity of muscular arteries compared with elastic arteries and/or differences in heterogeneous influences such as metabolic requirements and hydrostatic pressures.