What is the molecular biological basis of viral pathogenesis in the central nervous system (CNS), ie by what molecular mechanisms do different viruses produce particular patterns of neurological disease in man and animal models, and can one use molecular techniques to ascertain the viral aetiology of certain neurological conditions? This complex subject can be approached in three different but interrelated ways. First, one may relate molecular techniques to specific biological properties such as viral spread to the CNS, to neurotropism, ie the affinity of the virus for particular neural regions and cells, and to neurovirulence, which refers to the actual ability to cause neurological disease. Second, the reverse approach can be adopted by considering these different aspects of virus-host relationships and then how the techniques have contributed to their understanding. Third, one can select specific neurotropic viruses, such as polio or herpes viruses, and then relate these to both particular techniques and pathogenetic mechanisms [1]. The second component of this paper will deal with the immunopathological mechanisms seen in three specific CNS viral infections, all of which have been the focus of study in the author's laboratory over the past six years.