The inflammatory response in the central nervous system (CNS) of rats with differing susceptibility to demyelinating encephalitis induced by coronavirus MHV4 was characterized. Topographical maps showing the arrangement of infiltrating lymphocyte subsets in virus-infected tissue were developed by digital-image processing of immunohistologically stained CNS sections. The kinetics of the inflammatory process was evaluated by flow-cytometry on lymphocytes isolated from the CNS. Cumulative data obtained with these two techniques demonstrated the following features. In susceptible Lewis (LE) rats, viral antigens were disseminated throughout the CNS, including spinal cord. Onset as well as recovery from neurological disease was associated with a steep rise of infiltrating CD8+ T cells, which localized in close contact to virus-infected cells. Accompanying convalescence was a slight increase in B(OX33+) cells in the CNS and the accumulation of immunoglobulin-containing cells in the centre of virus-infected areas. In clinically resistant Brown Norway (BN) rats, virus-infected cells were mainly restricted to small periventricular foci and the extent of lymphocyte infiltration was never as high as that found at any time during the course of infection in LE rats. There were striking differences in the CD8+ T-cell population compared to LE rats. Cells of this phenotype were identified in virus-affected areas of BN rats only early after infection, and their infiltration profile revealed much lower quantities than in the CNS of susceptible LE rats. Although the population dynamics of B(OX33+) lymphocytes were comparable in BN and LE rats, as determined by flow-cytometry, less immunoglobulin-containing B cells were detected in virus-infected areas of BN rats.