BACKGROUND: Previous reports have noted that factor (F) XI and FXII and prekallikrein (the contact phase proteases) are absent in fish. OBJECTIVES: A broad survey of recently completed genomes was undertaken to find where during the course of vertebrate evolution these coagulation factors appeared. METHODS: BLAST searches were conducted for the various factors on genomes of lamprey, puffer fish, zebra fish, frog, chicken, platypus, and opossum. RESULTS: It was confirmed that FXII is absent from fish; it is present in frog, platypus, and opossum, but is absent in chicken, an apparent example of gene loss. A single gene corresponding to the evolutionary predecessor of FXI and prekallikrein occurs in frog, chicken, and platypus. The opossum (a marsupial) has both prekallikrein and FXI, completing the full complement of these genes that occurs in eutherian mammals. CONCLUSIONS: The step-by-step accrual of genes for these factors by a series of timely gene duplications has been confirmed by phylogenetic analysis and other considerations.