Chemokines are a family of structurally related chemotactic cytokines that regulate the migration of leukocytes, under both physiological and inflammatory conditions. CC chemokines represent the largest subfamily of chemokines with 28 genes in mammals. Sequence conservation of chemokines between teleost fish and higher vertebrates is low and duplication and divergence may have occurred at a significantly faster rate than in other genes. One feature of CC chemokine genes known to be conserved is genomic clustering. CC chemokines are highly clustered within the genomes of human, mouse, and chicken. To exploit knowledge from comparative genome analysis between catfish and higher vertebrates, here we mapped to bacterial artificial chromosome (BAC) clones 26 previously identified catfish (Ictalurus sp.) chemokine cDNAs. Through a combination of hybridization and fluorescent fingerprinting, 18 fingerprinted contigs were assembled from BACs containing catfish CC chemokine genes. The catfish CC chemokine genes were found to be not only highly clustered in the catfish genome, but also extensively duplicated at various levels. Comparisons of the syntenic relationships of CC chemokines may help to explain the modes of duplication and divergence that resulted in the present repertoire of vertebrate CC chemokines. Here we have also analyzed the expression of the transcripts of the 26 catfish CC chemokines in head kidney and spleen in response to bacterial infection of Edwardsiella ictaluri, an economically devastating catfish pathogen. Such information should pinpoint research efforts on the CC chemokines most likely involved in inflammatory responses.