Prosaposin is the precursor of saposins A, B, C and D, which are activators of sphingolipid hydrolases. In addition, unprocessed prosaposin functions as a neurotrophic factor in the central and peripheral nervous systems by acting to prevent neuronal apoptosis, to elongate neurites and to facilitate myelination. In this study, the expression pattern of prosaposin in the facial nerve nucleus after facial nerve transection was examined by immunohistochemistry and in situ hybridization. Prosaposin immunoreactivity in the neurons on the operated side facial nerve nucleus showed a biphasic pattern: it was significantly increased on day 3 after transection, decreased dramatically on day 7, started to increase gradually on day 14 and reached another peak on day 21 after transection. Significant increases in the levels of prosaposin mRNA were identified in the neurons on the operated side, suggesting that prosaposin was synthesized vigorously by the neurons themselves in the case of facial nerve transection. The diverse changes in prosaposin immunoreactivity during the process of facial nerve regeneration may reflect the diverse neurotrophic activities of prosaposin in facial motoneurons. © 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.