Microdialysis tubes, used for measurements of extracellular neurotransmitter concentrations, were implanted in rat dorsal hippocampus to study the adjacent tissue reaction. The brain was examined 1-60 days after the implantation. Within the first 2 days, normal neuropil and only occasional hemorrhage surrounded the microdialysis tube. Three days following the implantation astrocytes close to the dialysis tube, hypertrophied. Hypertrophic astrocyte processes invaded the spongy fiber wall. There was no increase in the number of astrocytes. Fourteen days after the fiber insertion layers of reticulin-positive fibers separated astrocytes and the remaining neuropil from the fiber wall. Late tissue changes (1 and 2 months) consisted of collagen deposits and occasional granuloma formation. These results can be used to predict the optimal time for commencing microdialysis after the fiber implantation.