We analyzed frozen brain specimens from three patients with subacute sclerosing panencephalitis (SSPE) for the presence of interleukin (IL)-1β, IL-2, IL-6, tumor necrosis factor (TNF), lymphotoxin (LT), and interferon (IFN)-γ using immunocytochemical techniques. We detected these cytokines in SSPE brain lesions demonstrating extensive cellular infiltrates, demyelination, and gliosis. Double-label immunocytochemistry, using cell-specific markers, showed that positive immunoreactivity for these cytokines was present on both infiltrating cells and resident brain cells. We also found IL-6, TNF, and IFN-γ at lower levels in brain tissue from a patient with progressive multifocal leukoencephalopathy. In contrast, normal control brain sections showed no reactivity for any of the cytokines. These findings indicate that IL-1β, IL-2, IL-6, TNT, LT, and IFN-γ may be produced in SSPE lesions and may be involved in the lesion pathogenesis of SSPE.