Multiple sclerosis (MS) is an immune-mediated demyelinating condition in which numerous soluble mediators have been implicated. We have extended the repertoire of cytokines studied in MS tissue by examining interleukin (IL-4), IL-6, IL-10, IL-12, IL-18, interferon (IFNgamma), and their receptors and have compared patterns with those seen in normal subjects and other neurological diseases (OND). Expression was evaluated by immunocytochemistry and Western blots. Remarkably, oligodendrocytes expressed all the cytokine receptors examined, particularly Th2-type, constitutively in normal subjects and upregulated in disease. Microglial cells also expressed cytokine receptors at similar levels. Cytokine expression was invariably a feature of microglial cells, except for IL-10, which was exclusively astrocytic. Oligodendrocytes did not display cytokines, except for low levels of IL-18. Although no pattern was specific for MS, most molecules were upregulated in MS and OND. Downstream JAK/STAT molecules were correspondingly upregulated. Cytokine receptors on oligodendrocytes (and microglia), and their corresponding ligands on microglia (and astrocytes), may implicate paracrine/autocrine regulation and may bespeak innate immunity in the central nervous system.