To assess the functional structure of prepro-melanin-concentrating hormone (pMCH), we isolated and cloned pMCH (of-pMCH) mRNA from the brain of the olive flounder, Paralichthys olivaceus, and compared its amino acid sequence with those from other animals. In addition, to examine whether activation of the brain of-pMCH gene is influenced by background color, density, and feeding, we compared pMCH mRNA activities against different background colors (bright and dark) and at different densities (100% PCA and 200% PCA). To examine whether the pMCH gene is related with malpigmentation of blind-side skin and appetite, we compared pMCH gene expression between ordinary and hypermelanic flounders, and between feeding and fasting flounders. The of-pMCH cDNA was 405 bp in the open reading frame [ORF] and encoded a protein of 135 amino acids; MCH was 51 bp in length and encoded a protein of 17 amino acids. An obvious single band of the expected size was obtained from the brain and pituitary by RT-PCR. In addition, of-pMCH gene activity was significantly higher in the bright background only at low density (< 100% PCA) making the ocular skin of fish whitening, and in ordinary fish. However, the gene activity was significantly decreased in dark background, at high density (>200% PCA), and in hypermelano fish. These results suggest that skin whitening camouflage of the flounder is induced by high MCH gene activity, and the density disturbs the function of background color in the physiological color change. Moreover, our data suggest that a low level of MCH gene activity may be related to malpigmentation of the blind-side skin. In feeding, although pMCH gene activity was significantly increased by feeding in the white background, the pMCH gene activity in the dark background was not influenced by feeding, indicating that the MCH gene activity increased by feeding can be offset by dark background color, or is unaffected by appetite. In conclusion, this study showed that MCH gene expression is related to ocular-skin whitening camouflage and blind-skin hypermelanosis, and is influenced by background color and density.