Major histocompatibility complex (MHC) antigen and glial fibrillary acidic protein (GFA) expression in rat brain was observed following 6-hydroxydopamine (6-OHDA)-induced lesions to the nigrostriatal tract. MHC class I and class II antigen expression was observed on cells, morphologically identified as monocytes/macrophages, at the injection site. MHC class I and class II antigen expression was also observed on reactive microglia, particularly in the region of degenerating SN neurons, but also along the nigrostriatal tract. Class I expression was more vigorous than class II. MHC class I expression appeared by day 1 and class II by day 4. Peak MHC expression occurred between day 6 and day 10. It subsided as healing took place and had largely disappeared by day 30. GFA expression in reactive astrocytes, on the other hand, developed early but was still prominent by day 90. MHC expression is reflective of immune system activity and occurs in conjunction with neuronal injury and disappearance. GFA expression is reflective of residual astrocytic scarring and remains after phagocytotic activity has been completed. Combined observation of these markers in diseased brain tissue can provide clues as to the stage of the pathology being observed.