The dynamics of pro-opiomelanocortin (POMC) biosynthesis in the adult rat are altered by demands imposed on the system, such that acute stress increases in the efficiency of anterior pituitary (AP) posttranslational events, while repeated stress increases pretranslational events. In contrast, the developing animal has a limited adrenocortical response to acute stress during the first 2 weeks of life (stress nonresponsive period). In this study, we investigated how the maturing AP and intermediate lobe (IL) POMC cells respond to repeated demand. Measurements of AP and IL POMC mRNA and POMC peptides were performed using Northern gels and radioimmunoassay, respectively. Plasma ACTH and corticosterone measurements were also performed. Maternal isolation, for 1 h on 3 consecutive days, was used as a repeated stress stimulus. The developing AP and IL exhibit an age-related increase in POMC mRNA and peptide levels. On the other hand, AP and IL do not respond to repeated intermittent maternal isolation during the first 2 weeks of life. However, a significant corticosterone release is seen in the 14 and 21-day-old animals. A change in POMC mRNA level is only detected in the 21-day-old AP where levels decrease. Therefore, an adrenocortical response to repeated intermittent maternal isolation predates the appearance of glucocorticoid inhibition of POMC expression in the 21-day-old animal. We propose that an immature neuronal inhibitory circuit during the 3rd week of life causes a sustained corticosteroid response which may in turn trigger AP-delayed feedback.