Neurochemical and morphological effects of repeated microdialysis or permanent microdialysis probe implantations in striatum were studied. The extracellular levels of dopamine did not change between a first and a second probe insertion separated by 2 weeks or at a third dialysis session 2 days later. The 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were similar at the first and second microdialysis session, but decreased at the third. Probes implanted permanently for 2 weeks clogged, and the recovery varied markedly after insertion of new probes. Tyrosine hydroxylase-stained dopamine fibers appeared unaffected after all dialysis sessions, although some swollen fibers were observed surrounding the probes. No change in the glial fibrillary acidic protein staining was seen immediately after the first dialysis session, although 2 weeks later gliosis was observed. After the second and third dialysis a diffuse gliosis was observed, while a glial barrier was seen surrounding the permanently implanted probes. Immediately after the first dialysis session enlarged laminin-stained blood vessels were seen, whereas repeated probe implantation also increased the blood vessel density. Thus, chronic in vivo microdialysis with permanently implanted probes is limited by severe technical problems and marked tissue changes. On the other hand, repeated probe insertion in the same brain site appears to be acceptable for performing chronic microdialysis studies in the same subject, provided neurochemical and morphological changes are taken into consideration.