We studied a family in which two infants had died with massive venous thrombosis shortly after birth. Protein C antigen was undetectable by immunologic assays of plasma available from one infant. (Protein C is a potent naturally occurring anticoagulant that inactivates activated coagulation factors V and VIII). The parents, who were first cousins, both had partial protein C deficiency. Reduced protein C levels were also observed in 12 of 25 additional family members. None of the partially deficient family members (age range 4 to 70 years) had thrombotic episodes. Our data support the view that hereditary protein C deficiency is an autosomal disorder in which the homozygous state may be manifested by the virtual absence of plasma protein C and by fatal thrombosis in the neonatal period.