Pituitary opioid peptides levels, measured by guinea-pig ileum bioassay, have been evaluated in rats given single intracerebroventricular injections of alpha-methyl-p-tyrosine (4 mg/rat) or phentolamine (40 microgram/kg). Phentolamine produces an immediate rise in corticosteroid levels and an increase in pituitary endorphin content after 20 min. alpha-Methyl-p-tyrosine does not affect the pituitary endorphin levels, even if its effectiveness as a stressing agent is demonstrated by serum corticosterone increase and by reduced hypothalamic norepinephrine concentration. Repeated steroid treatment results in a decrease of serum corticosterone levels and of pituitary opioid activity. Such a decrease is mainly due to the reduction of beta-endorphin content, as shown by gel filtration analysis of pituitary extracts. It is suggested that the pituitary endorphin system, like ACTH, is under negative direct or indirect regulatory control of glucocorticoids. The adrenergic inhibitory tonus on pituitary opioid peptides, however, requires further confirmation.