Two new families with history of thrombosis and high levels of histidine-rich glycoprotein (HRG) are described. The propositus of family 1 died of massive pulmonary embolism at age 34. Among his relatives, the mother and the maternal grandmother had suffered from deep and superficial vein thrombosis in their youth. A maternal aunt had several episodes of superficial vein thrombosis (SVT). High levels of HRG were found in the mother, three siblings and two nephews. In the second family, the proposita suffered from spontaneous deep vein thrombosis (DVT) at age 24. The paternal grandmother and a paternal aunt had several episodes of SVT and DVT. Also in this family, high levels of HRG cosegregated with thrombotic symptoms. These new families confirm that genetically transmitted high levels of HRG could be associated to familial and juvenile thrombophilia.