Human color vision is controlled by the red, green, and blue cone pigments. Their photo-absorption wavelengths spread uniquely over the three primary colors, although these pigments include common chromophore, retinal. In this study, molecular mechanism of color tuning in the cone pigments was clarified. The protein effect represented by the electrostatic potential is primarily important for the spectral tuning among the pigments. The structural distortion effect of the retinal chromophore is important in the human blue pigment. The result of the analysis indicates that amino acids at specific positions in the opsins regulate the color tuning. (C) 2008 Elsevier B.V. All rights reserved.