The prevalence of a patent foramen ovale was assessed by simultaneously performing transesophageal contrast echocardiography and transcranial contrast Doppler sonography (TCD) in 137 subjects (mean age 36 years) with stroke of unclarified etiology (n = 41), clarified etiology (n = 33), and in normal subjects (n = 63; mean age 32 years). Patent foramen ovale was found significantly more often in patients with unclarified than clarified strokes or in normal subjects (66% vs 33%, or 43%). Massive paradoxical embolism through a patent foramen ovale, identified by TCD, occurred significantly (p < 0.01) more often in patients with unclarified (64%) than clarified (27%) strokes or in normal subjects (3%). However, minimal shunts were typical in normal subjects (79%). Patent foramen ovale was detected indirectly by TCD when calculated on the basis of transesophageal contrast echocardiographic findings (sensitivity 89%, specificity 92%). Thus, TCD reliably detects paradoxical cerebral embolism through a patent foramen ovale, and provides important additional information for evaluating its clinical relevance by semi-quantification of embolic contrast material.