We examined whether central or peripheral administration of interleukin-1 beta (IL-1 beta) might change levels of nitric oxide (NO) and hydroxyl radical ((OH)-O-center dot) in the medial prefrontal cortex (mPFC). Extracellular levels of NO metabolites (NOx(-)) and 2,3-dihydroxybenzoic acid (2,3-DHBA), as a marker of (OH)-O-center dot production, were determined with an in vivo microdialysis technique in conscious rats. In the mPFC, central administration of IL-1 beta into the mPFC resulted in dose-dependent increases in levels of both NOx- and 2,3-DHBA. In contrast, peripheral administration of IL-1 beta significantly increased NOx- levels but not 2,3-DHBA levels. Perfusion of Mn(III) tetrakis (4-benzoic acid) porphyrin chloride, a superoxide (O-2(-)) dismutase mimic, into the mPFC reduced the increases in levels of 2,3-DHBA induced by centrally administered IL-1 beta, but enhanced the increases in levels of NOx- induced by centrally administered IL-1 beta. The present results show a different response in free radical productions in the mPFC between central and peripheral administration of IL-1 beta. This finding should be useful for our understanding of the response of NO and free radicals such as (OH)-O-center dot and O-2(-) in the mPFC after central and peripheral administration of IL-1 beta. (c) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.