In the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene a common 4G5G polymorphism was described. A 4G allele is associated with increased transcription of PAI-1 protein due to different binding of transcription regulating proteins than in 5G site. This may change the fibrinolitic capacity, decreasing the ability to lyse clots. Many studies showed that 4G5G polymorphism was associated with increased risk for cardiovascular disease. Still, conflicting data are reported for cerebrovascular disease, even suggesting protective role of 4G allele. In order to investigate relation between 4G5G polymorphism and stroke incidence, 52 stroke patients and 126 healthy subjects were genotyped by PCR-SSCP analysis. Genotype distribution among controls was: 4G4G 24% (30), 4G5G 48% (60) and 5G5G 29% (36). The allelic frequencies in control group were: 4G 48% and 5G 52%. In patients group the genotype distribution was: 4G4G 23% (12), 4G5G 40% (21) and 5G5G 37% (19). The frequencies for 4G and 5G alleles were 43% and 57%, respectively. There was no significant difference for genotype and allele frequencies between control and patient group (÷2 test). A trend towards a lower prevalence of the 4G allele in the patients group was observed (43% vs. 48% in control group, OR 0.8, 95% CI 0.53-1.32). These preliminary findings suggest that 4G allele is not a risk factor for stroke and may even be related to its reduced incidence. Further studies are needed on a larger number of subjects to evaluate the role of 4G allele in cerebrovascular disease.