Toll-like receptors (TLR) are relevant for piscine innate immunity. TLR activation recruits several downstream factors regulating the expression of immunorelevant genes. We have characterized two key factors of innate immunity from rainbow trout: MyD88 as an adaptor protein interacting directly with TLRs, and serum amyloid A as an effector molecule induced by the activated Toll-like receptor signaling cascade. Both factors share a remarkable high degree of structural conservation with their mammalian orthologs suggesting that innate immune defense mechanisms may also functionally be conserved between fish and mammals.