CD4+ T-cell lines with specificity for individual measles virus (MV) structural proteins were obtained from immunized Lewis rats. Isolated viral proteins, either purified from virions or bacterially expressed were used as antigens for immunological assays. All the cell lines secreted interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), but were only weakly cytotoxic to autologous MV-infected astrocytes. When cultured together with memory splenic B lymphocytes these T cells did not induce secretion of MV-specific antibodies. The in vivo function of the T-cell lines was investigated in our MV-encephalitis model in the Lewis rat. Within 24 hr of intracerebral infection, adoptive transfer of single MV protein-specific T cells either decreased or prevented the subsequent clinical and histological disease depending on the MV-protein specificity of the cell lines. Furthermore, there was an earlier and enhanced viral clearance from the CNS, without a change in the anti-MV antibody titres of serum and cerebrospinal fluid (CSF) of the recipients and the control-infected animals. Prior depletion of CD8+ T lymphocytes in the recipient animals did not abrogate the protection conferred by CD4+ T-cell lines, indicating that the acute viral CNS disease is being efficiently controlled by virus-specific CD4+ T cells.