Intracerebral microdialysis of awake rats was used to monitor the possible release of neurotrophic factors from brain cells in response to injury and excitation. Perfusates were tested with ganglia bioassays and enzyme immunoassay. Trophic activity was released after implantation of the microdialysis probe into the hippocampus but not into the striatum, as assessed by increased nerve fiber outgrowth from Remak’s ganglion. Kainic acid treatment significantly increased the release of trophic activity from hippocampal sites. These findings suggest that the brain responds to mechanical injury as well as to certain excitatory stimuli by regional extracellular release of neurotrophic activity that is not identical to the actions of known neurotrophic factors.