A common point mutation in the factor-V gene at the exact site (Arg 506) where activated protein C (APC) normally cleaves and inactivates the Va pro-coagulant accounts for APC resistance and is the most important genetic risk factor for venous thrombosis. It has also been suggested as a possible risk factor for stroke. We determined the prevalence of the Arg 506 Gln mutation in 180 patients (mean age 65.3 years) with cerebrovascular disease (138 stroke and 42 TIA) and compared it with that in 70 age-matched controls (mean age 64.9 years). The mutation was no more common in patients than controls [15/180 (8.3%) vs. 5/70 (7.1 %), p = 0,6]. Within the patient group there was no relationship between the presence of the mutation and age of stroke or the occurrence of TIA or stroke. There was no association between the mutation and any particular stroke subtype (large-vessel, lacunar, cardioembolic or unknown). The factor-V Arg 506 Gln mutation is not an important risk factor for stroke and TIA in an unselected group of patients, and routine screening is not justified.