Intrinsic Factor (IF) secretion was studied using isolated gastric mucosal cells from rat and man. In the rat, IF was localized to the chief cells and its secretion responded most efficaciously to carbachol. DbcAMP and hexoprenaline were less powerful, whereas histamine and pentagastrin lacked any effect. In man, IF secretion derived from the parietal cells and was increasingly enhanced by hexoprenaline, pentagastrin, carbachol, histamine and dbcAMP. In both species, IF secretion differs with respect to its cellular origin and the pattern of secretagogue control: IF release from rat chief cells is due to muscarinic receptor excitation, whereas IF release from human parietal cells responds predominantly to histamine-H2-receptor activation and seems to be mediated by the cAMP system.