The carbohydrate-deficient glycoprotein syndromes are a recently individualized group of genetic multisystemic disorders. A predominant feature is a severe involvement of the central and peripheral nervous system resulting in psychomotor retardation, seizures, ataxia, and, mostly after infancy, stroke-like episodes. The hallmark biochemical feature is a carbohydrate deficiency in a large number of serum glycoproteins. Because coagulation factors and inhibitors are also glycoproteins, we performed a systematic study of these factors and inhibitors in nine patients with carbohydrate-deficient glycoprotein syndrome. All showed a decreased activity of factor XI and of the coagulation inhibitors antithrombin III and protein C. In five of seven patients more than 1 y old, there was also a (less pronounced) decrease of protein S and of heparin cofactor II. This combined coagulation inhibitor deficiency could explain the stroke-like episodes occurring in these children.