Objective: The purpose was to assess the temporal changes in cardiac function and cerebral blood flow during postmenopausal administration of estrogen with and without progestogen. Study Design: Sixteen postmenopausal volunteers were assessed during estradiol plus sequential norethindrone acetate and placebo in two 12-week periods. Temporal changes were measured by magnetic resonance flow mapping 8 times. Results: Systemic vascular resistance was reduced during estradiol (–6.9%; P <.05), declined further during the addition of norethindrone acetate, and was accompanied by an increase in stroke volume (maximum increase, 5.2%; P <.05) without fluid retention. Both systolic (–5 mm Hg; P =.03) and diastolic (–3 mm Hg; P =.03) blood pressure were reduced during estradiol. Cerebral blood flow was reduced after 9 weeks of hormone replacement therapy (–37 mL/min; P =.01) but increased to baseline after the addition of norethindrone acetate. Conclusions: Sequential hormone replacement therapy is associated with changes in cardiac function, which are of therapeutic potential in cardiovascular disorders. Sequential hormone replacement therapy exhibits an overall neutral effect on cerebral blood flow. (Am J Obstet Gynecol 2001;184:41-7.)