Although many aspects of the regulation of acid secretion at the cellular level among different species remains controversial, certain concepts have emerged that span the differences between species, model systems and investigators. The paracrine, endocrine, neural and autocrine pathways mediate acid secretion by acting both directly on the parietal cell and indirectly via modulation of mucosal paracrine cell function. Studies with cells isolated from the acid secreting canine oxyntic mucosa indicate that gastrin and cholinergic receptors are present on parietal cells, somatostatin cells, and the histamine-enterochromaffin-like cell (ECL). Subtypes of these receptors are clearly important; the gastrin receptor on the ECL cell and parietal cell are "B" type CCK/gastrin receptors, whereas the receptor on the somatostatin cell is an A type CCK receptor. From the vantage point of studies in the canine oxyntic mucosa, the challenge is no longer to determine whether parietal, histamine or somatostatin cells have gastrin or muscarinic receptors but to establish the physiologic relevance of the specific actions (secretory, trophic or differentiative) of these receptor subtypes. Furthermore, the mechanisms integrating these paracrine, exocrine and neural elements require elucidation.