This report summarizes the documented cases of homozygous protein C deficiency in the United States and Europe. Procedures for diagnosing and treating this disorder (both initially and over the long term) have been compiled by a working party on homozygous protein C deficiency of the Subcommittee on Protein C of the International Committee on Thrombosis and Haemostasis. Homozygous protein C deficiency is an autosomal recessive disorder that usually manifests itself by purpura fulminans and, less commonly, by massive large vein thrombosis; severe diffuse intravascular coagulation also develops in these infants, and there is evidence of intrauterine thrombosis. For confirmation of homozygous protein C deficiency in a neonate with purpura fulminans or massive venous thrombosis, the infant should have undetectable protein C activity and both parents should be heterozygous for protein C deficiency. At the onset of symptoms, the initial treatment should be plasma (8 to 12 ml/kg every 12 hours) until all lesions have healed. Two modalities for long-term treatment are accepted as useful in these children: oral anticoagulant therapy or protein C replacement (fresh frozen plasma or prothrombin complex concentrate). Liver transplantation has been performed in only one child, with success. Oral anticoagulation (vitamin K antagonists, maintaining the prothrombin time from one and one-half to two times control values or at the International Normalized Ratio of 2.5 to 4.4) is our recommendation of choice for long-term treatment. With appropriate care, these children are able to be free of coagulopathy and live relatively normal lives.