Brain abscesses were produced in the rat by direct intracerebral injection of agarose beads laden with Staphylococcus aureus. The method proved to be easy, reproducible, effective and was associated with a low mortality rate. The histopathologic features of the experimental abscess are similar to other animal models and to human abscesses. The encapsulation of the lesion, macrophage/microglial response, astrocytic activation, and changes in the surrounding brain parenchyma were studied by immunohistochemistry. Edema, diffuse microglial activation and diffuse astrocytosis characterized the early reaction of the injected cerebral hemisphere. After day 10, edema subsided, and the microglial and astrocytic responses became restricted to the area around the lesion. Fibronectin deposition in the capsule preceded the appearance of myofibroblasts, which was concurrent with the beginning of collagen deposition on day 9. Hypervascularity of the capsule appeared as early as day 6 and persisted through day 28. This study suggests that brain abscess formation can be separated into three components: an initial period of edema and glial activation; an intermediate phase of neovascularization and fibronectin deposition; and a final phase of collagen deposition and progressive fibrosis. This new model offers an excellent paradigm for the analysis of neural tissue reaction and de novo fibrous tissue deposition.