Immune reactivity in the central nervous system (CNS) in multiple sclerosis (MS) can be fuelled by activated T lymphocytes sequestered in the brain and those entering systemically. The perivascular cuff of the inflammatory lesion consists predominantly of T cells and macrophages, while the hypercellular interface between normal and degenerating myelin is comprised mainly of macrophages and activated microglia. MHC class II+ cells are abundant in the hypercellular zone and expression of both the polymorphic and invariant chains of the molecule are expressed beyond the plaque edge in the white matter where the staining is restricted largely to microglia. Under carefully controlled staining conditions expression of MHC class II can be demonstrated on microglia in control white matter. Thus the immunological privilege of the CNS does not appear to preclude constitutive expression of MHC antigens or prevent the traffic of activated lymphocytes into the brain parenchyma. However, the antigens priming the immune reaction in the CNS in MS and the role of antibodies in the demyelinating process remain a matter for speculation and the exact mechanisms of demyelination are as yet unresolved.