The expression of the human growth hormone (hGH) gene is regulated by several transcription factors. Basal level transcription factors include TATA box-binding proteins, Sp1, USF and CTF/NF-1. The hGH gene is expressed only in pituitary somatotrophs, and the pituitary-specific GHF-1/Pit-1 protein is a potent transcriptional stimulator. Glucocorticoid and thyroid hormones, insulin, and GHRH which acts via cAMP, also control hGH gene transcription via trans-acting factors some of which are the hormone receptors themselves. Three transcription initiation sites were detected when hGH gene promoter activity was studied in a cell-free system. This system enabled us to delineate the respective role of some transcription factors and to propose a model that accounts for the basal, pituitary-specific, and hormonal control of hGH gene expression.