In large prospective studies, plasma fibrinogen levels have been shown to be an independent risk factor of vascular disease, including ischemic stroke. Elevated plasma fibrinogen in an individual could be due to the presence of predisposing genetic and/or environmental factors, such as smoking. Of the polymorphisms studies to date, the beta-fibrinogen-455 (beta-Fg-455) G-->A substitution in the 5' flanking region is associated with the most consistent difference in plasma fibrinogen levels in both case-control studies and in selected groups of healthy individuals. In order to further elucidate the role of the beta-Fg-455 G-->A substitution in determining fibrinogen levels and susceptibility to ischemic stroke in case-control population, including 104 individuals with verified ischemic stroke and 156 healthy individuals. Turbidimetriy assays were used to measure plasma fibrinogen levels of all samples. The beta-Fg-455 G-->A mutation was identified by the polymerase chain reaction followed by restriction enzyme digestion of the amplified DNA with HaeIII. The plasma fibrinogen level in patients with ischemic stroke [(3.51 +/- 1.09) g/L] was significantly higher than that in the control [(3.08 +/- 0.71) g/L] (P < 0.01). The A-allele is associated with elevated fibrinogen levels in both patients and controls. The plasma fibrinogen levels in controls with A-allele in elder people were higher than in younger people (P < 0.05). Those with A allele in males of ischemic stroke had significantly higher plasma fibrinogen levels in smokers than in non-smokers and ex-smokers (P < 0.05), but it was not significantly difference in subjects of GG genotype (P > 0.05). Our data demonstrates an association of the beta-Fg promoter A-455 allele with higher fibrinogen levels in the general population, and suggests that the A-allele may be a susceptible predictor of ischemic stroke, particularly in aging and smoking.