Optical analyses of biological processes in living animals are limited by a lack of unique optical properties among key molecules. To overcome this limitation we directly labeled biological events with bioluminescent proteins as reporter molecules. In these studies the expression of luciferase was linked to either a bacterial pathogen or to an inducible viral promoter. Infection of mice and expression from the viral promoter were monitored noninvasively using the photons transmitted through tissues of living mice as an assay of enzymatic activity indicative of expression. The effects of an antibiotic on bacterial infection was assessed in real-time. The inducible nature of the viral promoter was demonstrated in the skin of transgenic mice containing the promoterreporter construct. The use of bioluminescent reporters may permit spatial and temporal analyses of a wide variety of biological processes in living mammals.