The atrial natriuretic peptide (ANP) gene may underlie stroke susceptibility and sensitivity to cerebral ischemia in an animal model of stroke. The authors investigate its role in humans by genotyping a polymorphism (G664A) in 436 patients with ischemic cerebrovascular disease and 295 community control subjects. The frequency of this variant was similar in both groups and across the different stroke subtypes. The ANP gene G664A polymorphism is therefore unlikely to be an important risk factor for ischemic stroke in this population.