Evidence for the involvement of the sixth component of complement (C6) in normal blood coagulation is provided by the description of a coagulation abnormality in rabbits with a genetic C6 deficiency and by its correction with highly purified preparations of C6. Whole blood clotting time in glass or plastic was prolonged and prothrombin consumption was decreased in blood from the deficient animals. Other parameters of blood coagulation were normal, including prothrombin time, partial thromboplastin time, specific clotting factor activities, platelet factor III function, platelet count, and bleeding time. Clotting time and prothrombin consumption became normal when physiologic amounts of highly purified C6 were added to the deficient blood. Partial consumption of C6 hemolytic activity, with a time course similar to the consumption of prothrombin, was demonstrated during the clotting of normal human blood.