Aims: To elucidate the detailed mechanism of histamine production by Photobacterium damselae subsp. damselae. Methods and Results: Histidine decarboxylase and related genes of P. damselae subsp. damselae were cloned, and three open reading frames named as hdcT, hdcA and hisRS were identified. The hdcA gene encodes a polypeptide of 377 amino acids and is considered to be the pyridoxal-P dependent histidine decarboxylase. The hdcT gene is assumed to be a histidine/histamine antiporter, and the hisRS gene is considered to be a histidyl-tRNA synthetase. Recombinant Escherichia coli strains harbouring plasmids carrying the P. damselae hdc genes were shown to over-excrete histamine extracellularly. Northern blot analysis and quantitative RT-PCR revealed high levels of mono- and bi-cistronic transcripts of hdcA, hdcT and hisRS genes under conditions of low pH and histidine excess. Conclusions: The hdcA gene of P. damselae was constructed as an operon with putative histidine/histamine antiporter and histidyl-tRNA synthetase. Monoand poly-cistronic transcripts and acid induction were detected. Significance and Impact of the Study: This is the first report of cloning the histidine decarboxylase gene cluster in Gram-negative bacteria. Also, these genes were induced under acidic conditions and in the presence of excess histidine.