The neural membrane glycoprotein PrP (prion protein) has a key role in the development of scrapie and related neurodegenerative diseases. During pathogenesis, PrP accumulates in and around cells of the brain from which it can be isolated in a disease-specific, protease-resistant form. Although the involvement of PrP in the pathology of these diseases has long been known, the normal function of PrP remains unknown. Previous studies have shown that the PrP gene is expressed tissue specifically in adult animals, the highest levels in the brain, with intermediate levels in heart and lung and low levels in spleen. Prenatally, PrP mRNA has been detected in the brain of rat and hamster just prior to birth. In this study we have examined the expression of the PrP gene during mouse embryonic development by in situ hybridisation and observed dramatic regional and temporal gene expression in the embryo. Transcripts were detected in developing brain and spinal cord by 13.5 days. In addition, PrP gene expression was detected in the peripheral nervous system, in ganglia and nerve trunks of the sympathetic nervous system and neural cell populations of sensory organs. Expression of the PrP gene was not limited to neuronal cells, but was also detected in specific non-neuronal cell populations of the 13.5 and 16.5 day embryos and in extra-embryonic tissues from 6.5 days. This cell-specific expression suggests a pleiotropic role for PrP during development.