Recently, the HPA-1b (PlA2) polymorphism of the platelet glycoprotein IIIa has been suggested as a genetic risk factor for coronary artery disease. We conducted two case-control studies of 103 patients with ischaemic cerebrovascular disease (CVD) and 101 patients with ischaemic heart disease (IHD). The groups were matched for age, race and sex. No significant differences regarding selected risk factors (hypertension, diabetes mellitus, hypercholesterolaemia and smoking) were found between case patients and controls. Moreover, we investigated 286 normal individuals from the Mediterranean area. Genotyping of HPA-1 was performed by PCR-allelic specific restriction and single-strand conformation polymorphism analysis. The prevalence of HPA-1b was similar among case patients and controls (29.2% vs. 25.3% and 26.7% vs. 34.6% for CVD and IHD case-control studies, respectively). The HPA-1b allele was found in 36.4% of the normal population. Finally, the analysis of platelet function in nine controls with the three possible HPA-1 genotypes (three a/a, three a/b and three b/b) indicates that HPA-1b genotype does not modify either the in vitro platelet aggregation and activation profile, nor the GP IIb/IIIa interaction with fibrinogen or von Willebrand factor. Our results do not support the role of HPA-1b polymorphism as an inherited risk factor for arterial thrombotic disease.