SummaryAdenylyl cyclase activities were measured in mucosal 600g paniculate preparations from the fundic stomach of rats, dogs, rabbits and guinea pigs. In vitro incubation with prostaglandin E1 and NaF activated the enzyme in all species. Penta-gastrin and carbachol were ineffective activators in any of the species tested. Hista-mine activated mucosal adenylyl cyclase activity in the guinea pig but not in any of the other species tested. Histamine antagonists did not conclusively demonstrate the specificity of histamine activated adenylyl cyclase. Our results do not support the universal hypothesis that activation of adenylyl cyclase is the first step in the mechanisms of action of gastric acid secretagogues. Our findings do indicate that species variability and mucosal tissue heterogeneity constitute difficult problems that must be solved prior to the elucidation of the mechanisms of regulation of acid secretion.The authors are indebted to Mrs. Lily Chang for expert technical assistance. This research w...