Acute stress promotes the secretion of prolactin (PRL) and of proopiomelanocortin (POMC)-derived peptides, adrenocorticotropic hormone and β-endorphin, from the pituitary into the systemic circulation. The present study evaluates the influence of recurrent stress upon the biosynthetic activity of cells secreting these hormones in the rat. Chronic, intermittent, electrical foot-shock (3 mA 1 s duration, every 5 s for 30 min, twice daily) over a period of 1, 3 or 7 days caused an increase in messenger ribonucleic acid (mRNA) levels coding for POMC in the anterior pituitary. Maximally elevated mRNA levels were achieved after 3 days treatment (about 80% in excess of control values) which showed no further change at 7 days. These elevated levels of POMC mRNA were associated with increased levels of immunoreactive (ir)-β-endorphin in the adenohypophysis following 7 days of stress treatment. In contrast, this treatment did not significantly alter mRNA levels coding for PRL in the anterior pituitary. Similarly, POMC mRNA levels in the intermediate/posterior pituitary were also not significantly altered during exposure to repeated stress. Similar changes in the biosynthesis of the pituitary hormones were seen in rats suffering from chronic arthritic pain for 3 weeks: there was an approximately 80% increase in POMC mRNA levels in the anterior pituitary which was associated with an increase in the levels of ir-β-endorphin in this lobe and an increase in the plasma levels of ir-β-endorphin. In contrast, there were no changes in the levels of mRNA coding for PRL in the adenohypophysis. Moreover, levels of POMC mRNA and of ir-β-endorphin in the intermediate/posterior pituitary remained unchanged. It is concluded that although lactotrophic and corticotrophic cells of the adenohypophysis and corticotrophic cells in the intermediate pituitary respond similarly to acute stress stimuli with an increased secretion, the biosynthetic activity of these cells is differentially modulated under chronic st