A term infant had a life-threatening inferior venal caval thrombosis during the first 24 hours of life. The plasma from the infant and his mother was found to be resistant to activated protein C and to be heterozygous for the factor V mutation (FV Leiden) associated with this disorder. The presence of this hereditary disorder should be considered in infants with thrombosis and in infants with conditions predisposing them to thrombosis.