A traumatic injury to the rat brain is known to induce astrocyte proliferation and hypertrophy leading to astrogliosis. In addition, trauma also induces microglial proliferation in the brain. Since basic fibroblast growth factor (bFGF) is believed to play a role in mediating glial responses to brain injury, we examined the effects of bFGF administration on astrocyte and microglial proliferation and astrocyte hypertrophy resulting from a traumatic injury to the rat brain. Intracerebroventricular infusion of bFGF for 2 days prior to and following injury failed to alter glial reactivity. In contrast, a single intralesion injection of bFGF immediately after injury increased total cell division 2 and 5 days later, with an exclusive effect on glial fibrillary acidic protein-negative glia which consisted mostly of cells of macrophage-microglial phenotype. In addition, bFGF also enhanced injury-induced astrocyte hypertrophy. These results support a role for bFGF in macrophage-microglia proliferation and astrocyte hypertrophy following brain injury. They also suggest that alteration of injury responses of nonneuronal cells of the brain may be a potential side effect of intracerebral administration of bFGF.