To develop spatio-temporally controlled somatic mutagenesis in the adult mouse nervous system, we established transgenic mice expressing the tamoxifen-inducible Cre-ERT recombinase under the control of the mouse prion protein (PrP) promoter. Cre-ERT was expressed in most regions of the brain and in the retina of one transgenic line, whereas its expression was mostly restricted to the hippocampus and the cerebellum in another line. As tamoxifen efficiently induced Cre-mediated recombination in the various neuronal cell types expressing Cre-ERT in the brain of adult mice, the PrP-Cre-ERT lines should be valuable tools to study the functions of genes involved in neurodegenerative diseases or regeneration, and in complex processes such as behaviour, learning and memory. Some limitations of presently available reporter lines for Cre-mediated recombination in adult mouse CNS are discussed.