A method for bioluminescence imaging in an animal is provided. The method comprises providing a whole animal containing a transcriptionally active nucleic acid sequence encoding a Ca.sup.2+-sensitive polypeptide, which comprises a chemiluminescent protein linked to a fluorescent protein; and monitoring photons emitted by the Ca.sup.2+-sensitive polypeptide. The Ca.sup.2+-sensitive polypeptide comprises aequorin protein covalently linked to a YFP (yellow fluorescent protein) or RFP (red fluorescent protein), and the link between the two proteins functions to allow luminescence by energy transfer between the two proteins. The photons are monitored from deep tissues of the animal.