Copley hypothesised the existence of an endoendothelial fibrin lining of blood vessels; while the Rokitansky-Duguid hypothesis suggests that ongoing fibrin formation on the arterial wall contributes to atherosclerosis. We assessed in vivo fibrin turnover by measurement of plasma levels of cross-linked fibrin degradation products (D-dimer antigen) using a sensitive immunoassay, in 68 patients with extensive atherosclerosis (chronic peripheral arterial disease) compared to 239 controls (a random population sample in the same area). Plasma D-dimer levels were significantly higher in patients than controls (p<0.01) and correlated with clinical severity. We suggest that the plasma D-dimer level may be a useful index of intravascular fibrin turnover and of the ongoing contribution of thrombosis to arterial disease.