Experimental studies in laboratory animals have shown that estrogen reduces stroke severity, but the impact of hormone replacement therapy (HRT) on ischemic stroke severity in humans is not known. There are 2 broad, longterm objectives of this project. The first objective is to determine whether there are differences in stroke severity and outcome between women who are HRT users and women who are nonHRT users. The second objective is to determine whether any difference in these 2 groups is related to enhanced fibrinolysis. The Specific Aims of this proposal are 1) to compare the initial stroke severity in women who are users and nonusers of HRT, 2) to measure any differences in markers of the coagulation and fibrinolytic systems in the acute stroke period, and 3) to assess stroke outcomes in women based on poststroke use or nonuse of HRTs. Subjects for this prospective, observational study will be women admitted with acute ischemic stroke to an academic medical center. In the acute stroke period, initial stroke severity will be assessed using the NIHSS and markers of coagulation (prothrombin fragment F1,2 and thrombinantithrombin III complex) and fibrinolysis (plasminogen activator inhibitor type I) will be measured. Relevant historical and demographic data will be collected. At 3 months poststroke, neurologic impairment (NIHSS), functional status (Barthel Index and Modified Rankin), and quality of life (Stroke Impact Scale) will be assessed. The differences in initial stroke severity will be analyzed accounting for co-variates, and the 3month outcomes will be adjusted for initial stroke severity. This work will provide critical information for physicians prescribing HRT for women at risk for stroke and address whether it is safe to continue these medications in the sub-acute period after stroke. As a K23 proposal, this project will not only provide important clinical information, but is a natural extension of the candidate's previous experience with coagulopathies and stroke, now combined with the commitment to study the impact of stroke in women. This proposal will also provide critical transitional support in a mentored environment leading to the candidate's complete independence as a clinical investigator.