Gastrin is a trophic stimulant of the acid producing gastric mucosa. Experiments have been carried out in rats, in which chronic states of either low or high serum gastrin levels were induced by surgical manipulation or drug treatment. A relationship between circulating gastrin and a trophic effect could be demonstrated in the oxyntic mucosa, but not in the pancreas and small intestine. Endocrine cells in the oxyntic mucosa (the ECL cells and A-like cells) are among the target cells for the trophic action of gastrin. The functional significance of these two cell populations is unknown. There is much experimental evidence indicating that they are under functional as well as tropic control of gastrin. The vagus nerve also exerts trophic control on the oxyntic mucosa, including the endocrine cells within it. This could be demonstrated by one-sided truncal vagotomy which caused atrophy of the mucosa and hypoplasia of endocrine cells (notably the ECL cells) on the denervated side of the stomach. Conversely, portacaval shunt greatly increased the number of ECL cells. There was no hypergastrinaemia after portacaval shunt, and no trophic effect on other cell types in the oxyntic mucosa. The factors responsible for the ECL cell proliferation after portacaval shunting remain unknown. Tumours may arise spontaneously from the ECL cells. Such neoplasias have been described in Mastomys (Praomys natalensis) and in man. ECL cell hyperplasia and neoplasia in man, but not in Mastomys, are usually associated with hypergastrinaemia either as a result of a gastrin producing tumour or as a result of achylia (sometimes associated with pernicious anaemia). It is unlikely that gastrin alone is responsible for the neoplasia, though it is quite likely that long-standing hypergastrinaemia triggers or facilitates a sequence of events that ultimately leads to tumour formation, via diffuse ECL cell hyperplasia.