THE POMC gene encodes the complex precursor to a variety of biologically active, important neuromodulator and endocrine peptides. It is expressed in a variety of tissues in the mammal, but its main site of expression is the pituitary anterior lobe cortocotroph and intermediate lobe melanotroph. The POMC molecule is posttranslationally processed to different biologically active peptides in these two cell types, with ACTH, β-lipotropin, and β-endorphin being major products in the corticotroph and α-MSH, corticotropin-like intermediate lobe peptide, and acetyl-β-endorphin in the melanotroph (1). This array of different biological activities derived from the POMC molecule possibly necessitates the observed complex regulation of POMC peptide secretion and POMC gene expression in pituitary. Regulation of POMC peptide secretion has recently been reviewed in several places (2, 3). This review will deal primarily with the regulation of POMC gene expression in rat and mouse pituitary tissues, the species in which the majority of the work has been done although examples of other mammalian systems will be used where appropriate.