The synthesis and secretion of growth hormone (GH) by the somatotropic cells of the anterior pituitary is under complex hormonal regulation. The hypothalamic peptides, growth hormone releasing factor (GHRF) and somatostatin, respectively stimulate and block GH release. We have shown that treatment of primary cultures of rat anterior pituitary cells with GHRF stimulates transcription of the GH gene, as well as GH release, and that this reflects the response of pituitary cells in vivo. Gick et al. have shown a stimulation of GH mRNA levels in normal pituitary cells in response to GHRF. Because normal pituitary cells are the physiological target for GHRF and because they exhibit both transcriptional and release responses to the hormone, they provide a valuable system with which to examine the important possibility of a link between hormone synthesis and release in secretory cells. Using this system, we demonstrate here that GHRF stimulates GH gene transcription independently of GH release and, conversely, that other agents can stimulate GH release without affecting transcription of the GH gene.