After adrenalectomy, the plasma levels of adrenocorticotropic hormone (corticotropin, ACTH)/endorphin peptides in rats rise dramatically in the first 4 hr while pituitary peptide levels fall sharply. Eight hours after adrenalectomy, plasma levels are near control values again but they then increase continuously over the next 8 days. Proopiomelanocortin (POMC) mRNA levels in the anterior pituitary (quantitated by hybridization with cloned POMC cDNA) increase 2-fold in the first 24 hours, reaching 15- to 20-fold the control level 18 days after adrenalectomy. When dexamethasone is administered to rats 8 days after adrenalectomy, the above events are reversed. Plasma ACTH falls to control levels within 2 hr whereas anterior pituitary POMC mRNA requires 5 days of treatment for return to control levels. The levels of POMC mRNA in the neurointermediate lobe and the hypothalamus are not altered by either treatment. Adrenalectomy increases transcription of the POMC gene in the anterior pituitary approximately 20-fold and halves transcription of the growth hormone gene within 1 hr of operation. Administration of dexamethasone immediately after adrenalectomy suppresses the increase in transcription of the POMC gene and increases the transcription of the growth hormone gene. Transcription of the POMC gene(s) in the neurointermediate lobe is not altered by either of these treatments.