Multiple sclerosis (MS), a putative autoimmune disease of unknown etiology, is characterized by CNS perivascular inflammation, foci of demyelination, and elevated intrathecal production of oligoclonal IgG's. T and B cells, macrophages, and microglia are all implicated in contributing to the initiation and perpetuation of the disease. In this brief review we discuss the possible role of T cells, B cells, macrophages, and microglia in contributing to the initiation and perpetuation of inflammation and demyelination in MS. Data from the rodent model of MS, experimental allergic encephalomyelitis (EAE) supporting a immunological basis for the pathology of MS is noted. This paper discusses recent data suggesting an interaction of the above-mentioned cells, as well as serum and CSF proteins including complement and anti-myelin/oligodendrocyte antibodies, in the pathogenesis of MS and EAE. Additionally, this review describes each cell type including the clinical and experimental evidence for their contribution to the immunologically mediated pathology of MS. Following the description of the role of individual cells, there is consideration of: the possible interaction of cells with the blood brain barrier (BBB) under normal and pathologic inflammatory conditions; the traffic of cells into the CNS in inflammation; and the role of antigen presentation within the CNS in the initiation, and perpetuation, of the CNS immune response. Finally, the review suggests a role for T cells in the initiation, amplification, and possibly the termination of CNS inflammatory events with particular attention paid to the pattern of T cell activation and T cell cytokine production.