To evaluate the immunopathogenesis in Rasmussen's encephalitis, peripheral lymphocyte subsets and interleukin-6 analysis were performed in three patients. Magnetic resonance spectroscopy and diffusion-weighted magnetic resonance imaging were performed to assess neuronal injury in the affected hemisphere. Before initiation of immune therapy, percentage of cytotoxic T cells was found to be increased in peripheral blood obtained from patients compared with a group of age-matched normal control subjects. During follow-up, percentage of cytotoxic T cells returned to the normal ranges only in one patient who had an early functional hemispherectomy. All three patients had significantly increased interleukin-6 concentration in cerebrospinal fluid and serum compared with the mean values of patients with acute viral encephalitis. The magnitude of interleukin-6 response in the patients correlated with the neuronal loss and atrophy on magnetic resonance spectroscopy and diffusion-weighted magnetic resonance imaging studies. The patient, who had a fulminant course and an early hemispherectomy, had higher interleukin-6 concentration in cerebrospinal fluid and serum than those of the other two. Detection of an increased percentage of cytotoxic T cells in peripheral blood supports the presence of a T cell-mediated inflammatory pathogenesis in Rasmussen's encephalitis. However, elevated interleukin-6 response might reflect the magnitude of the inflammatory process in the affected hemisphere.