Although glial cell line-derived neurotrophic factor (GDNF) expression is low in the adult brain, its administration protects dopaminergic neurons against a range of insults, leading to the suggestion of a role in dopaminergic regeneration. If locally produced GDNF is to fulfil a role in dopaminergic regeneration after injury, it seems reasonable to hypothesize that its expression will increase after mechanical trauma. We have demonstrated that GDNF mRNA expression increases within 6 h of using a wire knife to injure adult mouse striatum. Expression doubles after 1 week and remains elevated for at least 1 month. Most GDNF expression is associated with haemosiderin-containing cells, indicating production by brain macrophages. GDNF production by macrophages may be essential for neural regeneration following CNS trauma.