The complement and coagulation systems in mammalian blood are composed of multiple components with unique domain structures, and are believed to be established by exon-shufflings and following gene duplications. To elucidate their origin in vertebrates, liver EST and 5'- and 3'-rapid amplification of cDNA ends (RACE) analyses were performed in lamprey, Lethenteron japonicum. For the complement system, thefactor I cDNA was cloned for the first time outside of the jawed vertebrates. Evidence for the C3/C4/C5, fB/C2 and MASP-1/MASP-2/C1r/C1s gene duplications was not found, suggesting that these duplications occurred in the jawed vertebrate lineage. In contrast, the coagulation factors VII and X, prothrombin and protein C-like cDNAs were identified, indicating that duplications among them predated the cyclostome-jawed vertebrate divergence. The genes for terminal complement components, coagulation factors XI and XII, or prekallikrein were not found, suggesting that the complement and coagulation systems of an ancestral vertebrate were simpler compared to their mammalian counterparts.