Gastric acid secretion in response to a number of agonists, active at H1 and/or H2-receptors, were measured in the gastrically and intestinally perfused cod. Histamine (D50 = 15 nmol/kg X h) was the most potent of the agonists tested. The H2-active agonists 4-methylhistamine (4-MeHi), Na-MeHi, and Na,Na-MeHi were about 25 times less potent than histamine in this in vivo model. Na,Na-MeHi was a partial agonist, while 4-MeHi and Na-MeHi elicited maximum responses similar to that of histamine. Dimaprit and impromidine, two highly selective H2-agonists, failed to stimulate acid secretion under basal conditions, and inhibited histamine-stimulated acid secretion. The H1-selective 2-MeHi and 2-pyridylethylamine (2-PEA) were essentially inactive. It is concluded that the cod gastric histamine receptor related to acid secretion is of the H2-class. It is not, however, identical to the mammalian gastric H2-receptor, and should be placed in a separate subgroup.