Patent foramen ovale (PFO) is found in 40% of patients with cryptogenic stroke. Many are treated with warfarin or aspirin. However the risk of stroke recurrence of systemic embolization in medically treated stroke patients with PFO is unknown. Option of PFO either percutaneous or surgical closure exists and the interest in these modalities is high without proven efficacy. The potential national cost will be enormous if these methods are used for all stroke patients with PFO. Therefore, before these procedures can be considered for routine use, there is a clear need to determine the rate of stroke recurrence or systemic embolization in medically treated stroke patients with PFO. Such a trial will be extremely costly. A solution is to use the structure of existing stroke trial, Warfarin Aspirin Recurrent Stroke Study (WARSS). This is an NINDS-funded multi-center trial to assess the efficacy of warfarin versus aspirin in reducing death or stroke after an initial stroke. Data on systemic embolization is also available In WARSS, 1,920 patients from 50 centers are randomly, double-blindly assigned to warfarin or aspirin and followed for a minimum of two-years. However, WARSS has no provision has no provision for PFO identification. Therefore, the study proposed for continuation PFO in Cryptogenic Stroke Study (PICSS), used WARSS structure in identifying cryptogenic stroke patients who will be solicited to undergo transesophageal echocardiography (TE) for PFO characterization. Any WARSS patients that undergo TE for clinical purposes are also enrolled. The hypothesis tested is: PFO is an important risk factor for stroke recurrence or systemic embolization in medically treated stroke patients which double the two-year rate of stroke recurrence or systemic embolization. Currently 43 centers participate and as of 01/31/97, 476 of 1,717 WARSS patients are enrolled. Since patients are randomized to warfarin or aspirin, the rate of stroke recurrence or systemic embolization on each agent may be compared. Trans echocardiography allows for assessment of other potential cardioembolic source (aortic arch plaques, spontaneous echo contrast, atrial septal aneurysm and valve strands). Therefore, pilot data on the natural history of medically treated stroke patients with these variables will also become available. Continued funding is requested in order to maximize PICSS enrollment, collect and analyze TE tapes, and to perform necessary analyses in order to achieve the aims set forth.