Using beta-amyloid precursor protein immunolabeling, we have detected axonal injury in experimental herpes simplex encephalitis. amyloid precursor protein-specific signals were found in the mouse brain as either puncta or axon-like structures. They appeared where infected neurons were undergoing apoptosis and Iba1-immunopositive microglia transformed themselves into macrophages. These results show, for the first time, that axonal injury, i.e., functional disturbance of the fast axonal transport, can take place during the course of acute viral encephalitis. (c) 2005 Elsevier B.V All rights reserved.