1 The role of putative neurotransmitters of the central nervous system in the central gastric antisecretory effect of prostaglandin E2 (PGE2) was investigated in pylorus-ligated rats. 2 Pretreatment of the rats with an intracerebroventricular (i.c.v.) injection of6-hydroxydopamine (6-OHDA) prevented the antisecretory effect of the i.c.v. administration of PGE2, whereas pretreatment with 5,6-dihydroxytryptamine (5,6-DHT) plus p-chlorophenylalanine (PCPA) had no effect.3 I.c.v.-administered phentolamine and idazoxan antagonized the inhibition of gastric secretion induced by i.c.v. PGE2, whereas prazosin, propranolol and sulpiride injected via the same route were ineffective. 4 Diphenhydramine, cimetidine, naloxone and theophylline, all administered i.c.v., did not modify the antisecretory effect of i.c.v. PGE2. 5 The results suggest that an activation of a2-adrenoceptors in the brain is involved in the central gastric antisecretory effect of PGE2, whereas neither central 5-hydroxytryptamine receptors, ,-or Padrenoceptors, D2-dopamine receptors, histamine or opioid receptors nor adenosine seem to play any role here.