Cathelicidins are antimicrobial peptides, well studied in mammals and found to be multifunctional proteins, important in the fight against bacterial invasion. Cathelicidins in fish have only recently been identified and little is known about their function and importance in the immune system of fish. In this study we have identified several novel cathelicidin proteins in far related fish species such as Atlantic cod (Gadus morhua) and Arctic charr (Salvelinus alpinus). Atlantic cod was found to have at least three cathelicidin genes of which two are nearly identical except for a nine-amino acid duplication in the antimicrobial peptide region. The predicted mature peptides of cod were found to be unusual peptides, made mainly of arginine, glycine and serine (RGS) residues and form a novel class of antimicrobial peptides. Cathelicidin in Arctic charr and brook trout (Salvelinus fontinalis) were found to have an exon deletion in the cathelin region of the protein, which would lead to the deletion of the predicted loop 2 of cathelin and its adjacent beta-strands. This is the first report of a deletion of a whole exon in the family of the cathelicidins. Infection of fish with pathogenic bacteria caused an upregulation of the expression of the cathelicidins in Arctic charr and Atlantic cod and indicates a role of these proteins in fish innate immunity.