Growth inhibitory factor (GIF) is a small (7 kDa), heat-stable, acidic, hydrophilic metallothionein (MT)-like protein. GIF inhibits the neurotrophic activity in Alzheimer's disease (AD) brain extracts on neonatal rat cortical neurons in culture. GIF has been shown to be drastically reduced and down-regulated in AD brains. In neurodegenerative diseases in humans, GIF expression levels are reduced whereas GFAP expression levels are markedly induced in reactive astrocytes. Both GIF and GIF mRNA are present at high levels in reactive astrocytes following acute experimental brain injury. In chronological observations the level of GIF was found to increase more slowly and remain elevated for longer periods than that of glial fibrillary acidic protein (GFAP). These differential patterns and distribution of GIF and GFAP seem to be important in understanding the mechanism of brain tissue repair. The most important point concerning GIF in AD is not simply the decrease in the level of expression throughout the brain, but the drastic decrease in the level of expression in reactive astrocytes around senile plaques in AD. Although what makes the level of GIF decrease drastically in reactive astrocytes in AD is still unknown, supplements of GIF may be effective for AD, based on a review of current evidence. The processes of tissue repair following acute brain injury are considered to be different from those in AD from the viewpoint of reactive astrocytes.