Transient global cerebral ischemia induces selective neuronal degeneration in the adult rat hippocampus, which is both preceded and accompanied by activation of microglia and astrocytes. Altered expression patterns of cytokines and growth factors might influence the postischemic neuron-glial interactions as well as the degenerative neuronal processes. Northern blotting of hippocampal tissue from ischemic animals revealed elevated levels of transforming growth factor beta-1 (TGF-beta 1) mRNA, and in the present in situ hybridization study we examine the endogenous expression and cellular localization of TGF-beta 1 mRNA in the adult rat hippocampus at various intervals following 10 min of global cerebral ischemia. Six hours after ischemia, a diffuse expression of TGF-beta 1 mRNA was found throughout the brain, which further intensified until Day 2 and thereafter subsided. In parallel, a massive increase of signal was observed in the hilus fascia dentata from Day 1 and in area CA1 from Day 2 to 4, both areas displaying selective neuronal degeneration. Peak levels of TGF-beta 1 mRNA were found in the hilus around Day 4, whereas expression in the CA1 area persisted through Day 21, the latest time point examined. A similar biphasic response, consisting of a transient, generalized reaction and a persistent lesion-associated activation in areas undergoing selective neuronal degeneration, was previously described for microglia and is reconfirmed in the present study. Cells of the microglial/macrophage lineage thus include the potent modulatory cytokine TGF-beta 1 in their potential repertoire of responses to both CNS activation and lesioning.