Teleosts are an evolutionarily appropriate model for studying immunology. The innate immune system of fish is the principal defense mechanism. The acquired immune system is less developed in fish than mammals. Nonspecific cytotoxic cells (NCC) are a key cell in the teleost innate immune response and are the equivalent of mammalian NK cells. NCAMP-1, a histone-like protein on NCC, is an active participant in the antibacterial immunity of teleosts as both a pattern recognition receptor and an antimicrobial peptide. Recombinant NCAMP-1 and NCAMP-1 from NCC granule extracts had specific antimicrobial activity against Escherichia coli and Edwardsiella ictaluri. NCAMP-1 was expressed on the membrane of NCC and could be up-regulated by calcium ionophore activation. In vivo infection of channel catfish with Edwardsiella ictaluri resulted in increased membrane expression of NCAMP-1 on NCC and cell trafficking from the anterior kidney to the spleen. NCAMP-1 is involved in antibacterial innate immunity of teleosts.