Neutralizing anti-tumor necrosis factor alpha (TNF-alpha) antibody treatment of mice infected with the neurotropic JHMV strain of mouse hepatitis virus showed no reduction of either virus-induced encephalomyelitis or central nervous system demyelination. TNF-alpha-positive cells were present in the central nervous system during infection; however, TNF-alpha could not be colocalized with JHMV-infected cells. In vitro, TNF-alpha mRNA rapidly accumulated following JHMV infection; however, no TNF-alpha was secreted because of inhibition of translation. Both live and UV-inactivated virus inhibited TNF-alpha secretion induced by lipopolysaccharide. These data show that TNF-alpha is not secreted from infected cells and indicate that if contributes to either JHMV-induced acute encephalomyelitis nor primary demyelination.