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Although 4% of cerebral infarcts in the young can be attributed to hematologic disturbances that predispose to thrombosis, the frequency of cerebral infarcts caused by prothrombotic states is not known. Recently, the association between cerebral infarction and deficiencies of elements of the natural anticoagulant system has been recognized. Thirty-six consecutive patients under 40 years of age with cerebral infarction of undetermined cause were prospectively studied. Quantitation of natural anticoagulants was done at least 3 months after the cerebral infarction. The following activity tests were performed, all by the chromogenic method: antithrombin III, protein C, plasminogen, tissue plasminogen activator, and inhibitor of tissue plasminogen activator. Protein S was quantified by the Laurell rocket method. All patients underwent a complete cardiological examination, including two-dimensional echocardiography, as well as four-vessel cerebral angiography. Some patients were also studied by transesophageal echocardiography. Of 36 patients, 17 were male, with a mean age of 28 years. Mean age for women was 25 years. Nine patients (25%; 5 women, 4 men) had a deficiency of one natural anticoagulant and constituted group I. In these patients, isolated protein S deficiency was detected in five cases (13.8%); in one case, we observed the association between protein S deficiency and antiphospholipid antibodies; and deficiency of protein C was seen in one case (2.7%), of antithrombin III in one case (2.7%), and of plasminogen in one case (2.7%). Instances of cerebral infarction without natural anticoagulant deficiency (group II) included 12 women and 15 men. There were no differences in clinical and radiological findings between the two groups. Considering the importance of prothrombotic state, especially caused by deficiency of protein S, in the development of cerebral infarcts, we suggest that it should be looked for in every young patient affected by this pathological entity and in whom no etiologic factors can be determined.