A number of studies have signified the importance of neurons in the pathogenesis of the acute as well as chronic forms of MHV-induced neurologic disease in rodents. Following intranasal inoculation, MHV strains A59 and JHM invade the murine CNS by way of the olfactory and trigeminal nerves.1,2,3 Accordingly, interneuronal spread was hypothesized to be the most likely mechanism to explain viral CNS penetration by this route. Subsequent spread to other CNS regions was shown to also involve specific neuronal populations and tracts 2,4 Immunohistochemistry and in situ hybridization have demonstrated tropism of MHV-A59 for neurons within the olfactory nuclei, nuclei of the amygdala, central tegmental nucleus, entorhinal cortex, subiculum, claustrum, lateral habenular nucleus, subthalamic nucleus, basal ganglia, substantia nigra and septal nuclei among others in mice2,5 and of JHMV for hippocampal and cerebellar Purkinje neurons in rats.6,7 Although JHMV inoculated rats can develop a delayed onset, demyelinating encephalomyelitis with no prior evidence of acute encephalitis, histopathological and in situ hybridization studies have implied that clinically silent neuronal involvement likely precedes the development of the more chronic, demyelinating form of disease6,8 In addition to their potential importance as vehicles for MHV penetration and spread and as targets for cytopathic processes, neurons may also serve as reservoirs for viral persistence. The suggestion has been made that neurons may in fact be particularly well suited for this, due to insufficient expression of MHC class I molecules on their surfaces thus enabling them to avoid recognition by virus specific cytotoxic T cells.9 For these reasons, studies focusing on the interactions between neurotropic strains of MHV and rodent neurons should enhance our understanding of neuropathogenic mechanisms in a fundamental way.