The metabolism of cyclic AMP and HCl secretion has been studied in eight healthy volunteers, in eight duodenal ulcer (DU) patients, and in four pernicious anaemia patients. Pentagastrin showed a tendency to increase adenylate cyclase and cyclic nucleotide phosphodiesterase activities in the fundal mucosa and caused a significant increase in cyclic AMP output into the gastric juice in healthy volunteers and in DU patients. Cimetidine inhibited all these events but had no effect on basal cyclic AMP output. Vagotomy significantly inhibited basal cyclic AMP output. We conclude that cyclic AMP is involved both in basal and in pentagastrin-stimulated gastric secretion in man. Basal secretion is mainly controlled by vagal tone. The main pathway for this stimulus at the parietal cell may be via other than H2-receptors, probably through acetylcholinergic receptors. However, a significant part of the pentagastrin stimulation of the human parietal cell is via H2-receptors.