We investigated the association between cerebral venous thrombosis and hereditary resistance to activated protein C (APC) in 12 consecutive German patients with non-fatal cerebral venous thrombosis and in 187 controls without a history of thrombotic disorder. Three patients (25%) had a mutation in the factor V Leiden gene against only one subject in the control group. This difference was significant (P< 0.05), with an odds ratio of 11.7 (1.5-87 ; 95% confidence interval). Two patients carrying the mutation had additional common risk factors for thrombosis, and 2 had a positive family history of thromboembolism. We conclude that inherited APC resistance by a mutation in factor V Leiden is an important risk factor in non-fatal cerebral venous thrombosis. We recommend testing for APC resistance and, if abnormal for factor V Leiden mutation in patients with cerebral venous thrombosis.