Growth inhibitory factor (GIF) is down-regulated in Alzheimer's disease (AD) brains. To analyze the mechanism of this down-regulation, we isolated the human and mouse GIF genes. These genes consist of three exons, are approx. 1-kb long and show strikingly high homology to metallothionein-encoding genes. A comparison of the human and mouse GIF showed several conserved sequences, including the putative AP-2, SP-1, TATA-binding protein and metal-responsive elements (MRE). A sequence similar to the human gfa common sequence (hgcs), recently identified as the sequence for an astrocyte-specific transcriptional factor, is present in the promoter of these GIF. Characterization of factors associated with the putative regulatory elements in the promoter of GIF should help in determining the mechanism of the down-regulation of GIF in AD brains.