1. Prostaglandin E(1) inhibits basal and pentagastrin-stimulated gastric acid secretion. The mechanism of this action is not clear. One possible explanation might be that prostaglandin E(1) interferes with the local release or synthesis of histamine which has been proposed as the mediator of the effects of gastrin on the parietal cell.2. A single injection of prostaglandin E(1) did not affect mucosal histamine content or histidine decarboxylase activity in the rat stomach. Pentagastrin lowered the histamine content and activated the histidine decarboxylase to the same extent in prostaglandin E(1)-pretreated and in control rats. We conclude therefore that the inhibitory effect of prostaglandin E(1) on basal and pentagastrin-stimulated acid secretion is not caused by inhibition of histamine release or histamine synthesis.3. Repeated injections of prostaglandin E(1) resulted in a significant elevation of the gastric histidine decarboxylase activity in normal but not in antrectomized rats. Conceivably, this increase in enzyme activity is secondary to prostaglandin E(1)-induced inhibition of acid secretion, which will stimulate release of gastrin due to the rise in intragastric pH.