Improvement in endothelial function may be an important mechanism by which hormone replacement therapy (HRT) protects postmenopausal women against coronary artery disease. Our aim was to assess the effects of HRT on plasma nitric oxide (NOx) (nitrate plus nitrite) and total thiols in postmenopausal women, as these parameters are associated with enhanced endothelial functions. Thirty-five healthy postmenopausal volunteers (mean age 50.5 +/- 4.7 yr) in an academic and hospital research environment were involved in the study. Blood samples were collected, one at baseline and the second after 6 mo of HRT. Plasma NOx and total thiol levels were significantly elevated in the subjects after HRT. NOx may be of importance in the protective effects of HRT. Further, the increase of plasma antioxidant thiol levels might also contribute to the beneficial effects of HRT.