After intracerebroventricular (i.c.v.) injection of a missense oligodeoxynucleotide (MS-ODN) solution in rats, transcripts of the proinflammatory cytokine interleukin (IL)-6 were induced in hypothalamus, hippocampus, cortex and spleen and increased levels of circulating IL-6 and corticosterone were detected. Moreover, using a biotelemetric method body temperature of rats injected with ODN or Ringer solution was monitored over a period of 24 h after the injection. The i.c.v. injection of ODN induced a fever response which peaked at 6 h post-injection. These observations demonstrate that central administration of ODNs generates an inflammatory response in the central nervous system (CNS) and in the periphery as well.