To better elucidate the possible role of the patent foramen ovale (PFO) in patients with unexplained stroke, the relation between the incidence of stroke and 3 characteristics of PFO (timing, magnitude of appearance of echocardiographic contrast in the left atrium, and morphology of the atrial septum) was analyzed. Twenty-nine patients with unexplained stroke and 28 without stroke were compared. A significant relation was only found between the incidence of cerebrovascular accident and positive contrast echocardiography in patients with early and massive passage of contrast in the left atrium (6 of 29 [21%] in the stroke group vs 0 of 28 [0%] in the control group; p < 0.05). An abnormal morphology of the foramen ovale was found more frequently in patients with PFO than in those without PFO (9 of 13 [69%] vs 1 of 44 [2%]; p < 0.001). The results suggest the use of timing and quantification of contrast appearance in the left atrium during contrast transesophageal echocardiography, and that paradoxical embolism through a PFO is a possible mechanism of cryptogenic stroke only if there is a massive passage of contrast through an abnormal foramen ovale.