Astrocytes are involved, as are microglia/macrophages [Marty et al. (1991) Neuroscience 45, 529-539], in the formation of a glial scar after CNS lesions. This study was undertaken to follow the time-course of changes in the morphology and distribution of astrocytes that takes place during the formation of a glial scar after kainic acid injection in the rat thalamus. The astrocytes were identified using an antibody raised against glial fibrillary acidic protein (GFAP) and the progression of their reaction to the lesion was followed from 24 h to one year after the kainate injection. Three periods could be distinguished during the evolution of the astrocytic response in the neuron-depleted area. There was an initial appearance of a large number of GFAP+ cells. These cells displayed profound morphological differences from the normal. They were enlarged, round and devoid of processes. These GFAP+ astrocytes disappeared four days after the lesion. This increase of the GFAP+ cells in the neuron-depleted area may be due to cytoskeletal changes and thus an increased exposure of antigenic sites. In a second period between four and 14 days, the only GFAP+ elements present in the neuron-depleted area were long and straight processes. These processes entered the lesioned area from the periphery and seemed to follow axon bundles. Additionally, during the first weeks, the number of reactive astrocytes increased in a small band just around the area of neuronal loss. The third period began after two weeks. The lesioned area became gradually occupied by GFAP+ astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)