Objective: To assess serum. vascular endothelial growth factor (VEGF) concentrations in healthy postmenopausal women in relation to hormone replacement therapy (HRT) and the presence or absence of a uterus. Design: Cross-sectional study. Setting: The Middlesex Hospital. Patient(s): A total of 199 postmenopausal women were enrolled: 132 had uterus in situ and 67 had had hysterectomies. Of the 67 women who had had hysterectomies, 6 received no HRT, 20 received tibolone, 25 received transdermal E-2, and 16 received conjugated equine estrogens. Of the 132 women with uteri in situ, 34 received no HRT, 56 received tibolone, 24 received transdermal E, with sequential norethisterone acetate, and 18 received conjugated equine estrogens with sequential levonorgestrel. Intervention(s): Serum. VEGF level measurement. Main Outcome Measure(s): Serum. VEGF concentrations. Result(s): Women who received HRT had higher VEGF concentrations than those not receiving HRT. Among women who received no HRT, those with uterus in situ had higher VEGF levels than did those who had had hysterectomies. Among women who had had hysterectomies, VEGF concentrations were higher in those who received conjugated equine estrogens than in those who did not receive HRT and those who received tibolone or transdermal E-2. Among women with uterus in situ, no difference was found between subgroups. Conclusion(s): Postmenopausal women with uterus in situ and those who received HRT had higher VEGF concentrations than did those who had had hysterectomies and who did not receive HRT. Among women receiving HRT, those who received conjugated equine estrogens alone had higher VEGF concentrations. This estrogen-mediated increase in serum VEGF concentrations may be a mechanism by which HRT benefits the cardiovascular system (Fertil Steril(R) 2000;73:56-60. (C) 1999 by American Society for Reproductive Medicine.)