After the inoculation of a highly attenuated strain of herpes simplex virus (HSV) type 1 into the mouse hind-paw planter skin, a few neurons and glial cells were viral antigen-positive in the dorsal root ganglia (DRGs) and anterior horn of L4 and L5 segments of the lumbar spinal cord. Fos-containing nuclei, however, were not found in the DRGs or the lumbar cord segments. After the inoculation of a highly neuroinvasive strain of HSV type 2, many virus-positive neurons and glial cells were detected in the DRGs, anterior and posterior horns at L4 and L5; Fos-containing nuclei were also observed in spinal neurons except for motoneurons. The results indicate that transneuronal infection of HSV induces Fos expression in spinal neurons.