Fish losses from infectious diseases are a significant problem in aquaculture worldwide. Therefore, we investigated the ability of cationic antimicrobial peptides to protect against infection caused by the fish pathogen Vibrio anguillarum. To identify effective peptides for fish, the MICs of certain antimicrobial peptides against fish pathogens were determined in vitro. Two of the most effective antimicrobial peptides, CEME, a cecropin-melittin hybrid peptide, and pleurocidin amide, a C-terminally amidated form of the natural flounder peptide, were selected for in vivo studies. A single intraperitoneal injection of CEME did not affect mortality rates in juvenile coho salmon infected with V. anguillarum, the causative agent of vibriosis. Therefore, the peptides were delivered continuously using miniosmotic pumps placed in the peritoneal cavity. Twelve days after pump implantation, the fish received intraperitoneal injections of V. anguillarum at a dose that would kill 50 to 90% of the population. Fish receiving 200 g of CEME per day survived longer and had significantly lower accumulated mortalities (13%) than the control groups (50 to 58%). Fish receiving pleurocidin amide at 250 g per day also survived longer and had significantly lower accumulated mortalities (5%) than the control groups (67 to 75%). This clearly shows the potential for antimicrobial peptides to protect fish against infections and indicates that the strategy of overexpressing the peptides in transgenic fish may provide a method of decreasing bacterial disease problems.During the last decades, gene-encoded cationic antimicrobial peptides have been identified in virtually all species of life, including bacteria, plants, vertebrates, invertebrates, and mammals. Many of these peptides have been shown to play roles in host defenses, providing local nonspecific protection against infectious microbes. Such a role is assisted by the broad spectrum of activity against bacteria, fungi, and/or enveloped viruses and the rapid action of these cationic peptides. Wellknown examples of cationic antimicrobial peptides are the cecropins, melittins, magainin, and defensins (8).Protection of fish against infectious diseases is a major challenge in aquaculture worldwide, and losses due to infectious diseases limit profitability. The use of antibiotics and vaccination has partially alleviated this problem. However antibiotic use has raised concerns of antibiotic resistance development and antibiotic residues in fish. Vaccines are not available for all of the fish pathogens, and vaccinations can involve stressful handling of the animals. One alternative strategy would be to develop disease-resistant fish strains. Considerable evidence has shown that the ectopic expression of genes encoding peptides with in vitro antimicrobial activity can result in increased resistance to fungal and bacterial pathogens in transgenic plants (2,9,12,20) and mice (18). Those peptides could prove to be useful tools for the genetic engineering of disease resistance in transgenic fish. Ke...