The present study was attempted to investigate whether pentazocine, which is known to possess both opioid agonistic and antagonistic properties, produces catecholamines (CA) secretion from the isolated perfused rat adrenal gland, and to establish the mechanism of its action, and also to compare its action with that of some opioids. Pentazocine (30 to 300 ug) injected into an adrenal vein caused a dose-dependent secretory response of CA from the rat adrenal medulla. The pentazocine-evoked secretion of CA was remarkably diminished by the preloading with chlorisondamine (10^-6 M), naloxone (1.22 × 10^-7 M), morphine (1.7 × 10^-5 M), met-enkephalin (9.68 × 10^-6 M), nicardipine (10^-6 M) and TMB-8 (10^-5 M) while was not influenced by the pretreatment of pirenzepine (2 × 10^-6 M). The perfusion of Ca⁺⁺-free Krebs solution for 30 min into the gland also led to the marked reduction in CA secretion evoked by pentazocine. Furthermore, the CA release evoked by ACh and/or DMPP was greatly inhibited by the pretreatment with pentazocine (1.75 × 10^-4 M) for 20 min. From these experimental results, it is thought that pentazocine causes markedly the increased secretion of CA from the isolated perfused rat adrenal medulla by a calcium-dependent exocytotic mechanism. The secretory effect of pentazocine appears to be mediated through activation of opioid receptors located on adrenal chromaffin cells, which may be also associated with stimulation of cholinergic nicotinic receptors.