THE specific expression of growth hormone (GH) in the somatotrophic cells of the anterior pituitary is largely attributable to a short promoter in the 5' flanking region of the GH gene^1–6. This promoter contains two binding sites for the transcription factor GHF-1 (refs 3,7), the expression of which is also specific to cells of the somatotrophic lineage^8,9 and correlates with activation of the GH gene in the developing mouse pituitary⁹. Various studies indicate that GHF-1 is the main determinant of cell type-specific expression of the GH gene^3–9. GHF-1 is a member of the POU-domain class of proteins that each contain two highly conserved sequence motifs, the homoeodomain and the POU-specific domain^8,10,11. Here we report that the GHF-1 homoeodomain is sufficient for sequence-specific DNA binding, although its activity is stimulated by the POU-specific domain, which does not interact directly with the DNA. Transcriptional activation is mediated by a separate domain rich in hydroxylated amino-acid residues. Similar sequences are present in other cell type-specific transcription factors.