In situ hybridization was used to study the effect of IL-1 beta on acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) mRNA expression in rat brain. Intraventricular injection of recombinant human IL-1 beta did not affect hybridization to aFGF mRNA but did induce significant and widespread increases in hybridization to bFGF mRNA. IL-1 beta induced increases in bFGF mRNA were bilaterally distributed and appeared to correspond with the distribution of non-neuronal cells. Thus, hybridization was increased in regions of both gray and white matter (e.g., corpus callosum), the ependymal lining of the third ventricle, and the pia matter. In hippocampus of IL-1 beta injected rats, hybridization was markedly increased in the molecular layers but not significantly increased in the neuronal cell layers. Elevations in bFGF mRNA were transient, peaking at 8 h postinjection in most areas. To determine if IL-1 beta effects were independent of activation of the hypothalamo-pituitary-adrenal axis, and to compare the cellular localization of increases in bFGF mRNA expression induced by IL-1 beta and bFGF, the regulation of bFGF expression was also studied in organotypic hippocampal slice cultures. Treatment of cultures with either IL-1 beta or bFGF stimulated the same general distribution of increases in bFGF mRNA as seen after IL-1 beta treatment in vivo with an additional effect on immature neurons within the hilar side of stratum granulosum; hybridization of bFGF mRNA was not increased in association with the more mature neurons of stratum pyramidale or stratum granulosum. Colocalization of bFGF cRNA hybridization with immunostaining for glial fibrillary acidic protein demonstrated that increases in bFGF mRNA induced both by IL-1 beta in vivo and in vitro and by bFGF in vitro were largely associated with astroglial cells. These findings suggest that IL-1 beta induction of bFGF contributes to the coactivation of these substances following various forms of insult to the CNS and initiates a cascade of trophic interactions that regulates processes of glial proliferation, neurotrophic factor expression, and neuroprotection.