The characteristics and differences between DMPP and McN-A-343 on the secretory effect of catecholamines(CA) were studied in the isolated perfused rat adrenal glands. DMPP(100 uM) and McN-A-343(100 uM) perfused into an adrenal vein of the gland casued significant increases in CA secretion. On molar basis the secretory effect of McN-A-343 was about one fifth as potent as that of DMPP. Tachyphylaxis to releasing effects of CA evoked by DMPP and McN-A-343 was not observed by repeated perfusion of these agents. The DMPP-evoked CA secretion was significantly inhibited by pretreatment with chlorisondamine, desipramine and profusion of Ca2+-free Krebs solution containing EGTA, while it was not affected by pirenzepine, ouabain and physostigmine. However, pretreatment with atropine rather enhanced CA release by DMPP. The releasing effect of CA induced by McN-A-343 was markedly depressed by pretreatment with atropine, pirenzepine, chlorisondamine, physostigmine, and perfusion of Ca2+-free medium plus EGTA but was not influenced by desipramine, except for the case of ouabain which clearly potentiated CA release by McN-A-343. These experimental results suggest that both DMPP and McN-A-343 cause greatly secretion of CA from the isolated perfused rat adrenal glands by a calcium-dependent exocytotic mechanism. The secretory effect of DMPP is due to the stimulation of cholinergic nicotinic receptors and the secretion by McN-A-343 via activation of selecive M1-muscarinic receptors in the adrenal gland. It is also thought that the DMPP-evoked secretory effect is much greater than McN-A-343-induced effect.