The human complement system is composed of more than 30 serum and cell surface components, and most of these components show a characteristic domain structure, enabling us to trace the evolution of the genes based on their structures. Ongoing genome projects in both vertebrates and invertebrates revealed that most domains used by mammalian complement components are found in both protostomes and deuterostomes. However, the unique combinations of them as found in mammalian complement components are present only in deuterostomes, indicating that the complement system was established in the deuterostome lineage. Unexpectedly, the complement system of an invertebrate deuterostome, ascidian, shows a similar level of complexity as that of mammals. However, phylogenetic analysis suggested that expansion of complement genes by gene duplications occurred independently both in the ascidian and vertebrate lineages. Although most characteristic domain structures of the mammalian complement components are found in ascidians, detailed evolutionary analysis casts doubt on their mutual reactivity. Thus, the vertebrate complement system seems to be established by integrating some independent parts into one reaction system.