The concentration of ACTH and corticosterone in plasma were measured following peripheral administration of naloxone and naloxone methylbromide (quaternary derivative of opiate antagonist naloxone which is thought not to cross the blood brain barrier) in male rats. Subcutaneous administration of naloxone methylbromide in the dose range of 0.625 - 5.0 mg kg-1 resulted in a small but significant increase in plasma corticosterone levels. Both naloxone and its quaternary derivative injected via permanent intraperitoneal catheters to freely moving rats induced a highly significant increase in plasma ACTH levels measured in blood obtained via permanent tail artery catheters 30 min following injection. These results indicate that loci outside the blood brain barrier are, at least partially, involved in the naloxone-induced stimulation of ACTH release.