Stress-induced activation of secretion of ACTH and beta-endorphin (beta-END) from anterior lobe corticotrophs leads to both short term and longer term perturbation of the system. Immediately following an acute stress session, the rate of translation of the ACTH/beta-END precursor proopiomelanocortin appears accelerated by 50% and the rate of conversion of the precursor into products is doubled. These changes appear to take place at the translational and posttranslational level and reflect a better use of the preformed messenger RNA which compensates for the stress-induced peptide depletion. When the animal is subjected daily to the stress session, longer term mechanisms appear to emerge. The ACTH/beta-END stores in the gland are increased, apparently owing to an increase in transcription, as reflected by a small but significant increase in proopiomelanocortin messenger RNA. The posttranslational processing is no longer accelerated after further stress. This longer term mechanism appears to be pretranslational and to supplant the posttranslational mechanisms observed after acute stress. These two levels of control may represent different points in the regulation of this critical peptide system.