SUMMARY In normal, duodenal ulcer, and gastric ulcer subjects the two main forms of gastrin, GI 7 and G34, were estimated by radioimmunoassay in fasting serum and after feeding. Two antisera were used: one showing high specificity for G17, the other specific for the common COOH-terminus of G17 and G34 and so allowing estimation of G34 by difference. Basal G17 was similar in gastric ulcer, duodenal ulcer, and normal subjects and the increases of G17 after feeding were also similar in these groups. In contrast, basal G34 was similar in normal and duodenal ulcer subjects but raised in gastric ulcer subjects. After a meal the G34 concentration in both gastric and duodenal ulcer patients was significantly higher than normal. It is concluded that the higher post-prandial gastrin responses in peptic ulcer that have been previously described are due largely to increased G34.It is established that gastrin is responsible for the fulminating peptic ulceration seen in patients with the Zollinger-Ellison syndrome (Gregory et al., 1967). However, the importance of gastrin in the pathogenesis of peptic ulcer not associated with gastrinoma is unclear. Patients with both duodenal (Trudeau and McGuigan, 1970;Walsh and Grossman, 1973) and gastric ulcer (Korman et al., 1972) have higher than normal gastrin responses to a meal. However, patients with duodenal ulcer tend to have higher than normal basal and maximal rates of gastric acid secretion, whereas gastric ulcer patients have lower than normal basal and maximal acid outputs (Wormsley and Grossman, 1965). Interpretation of these findings is complicated by the fact that gastrin circulates in several different molecular forms, and that frequently the antibodies used in gastrin radioimmunoassays (RIA) are unable to distinguish between these forms (Walsh, 1974;Stadil et al., 1975). After a meal two forms of gastrin predominate in the circulation. These correspond to peptides with 34 amino-acid residues (big gastrin, G34) and 17 amino-acid residues (little gastrin, G17), that have been isolated from human 'Address for correspondence: Dr G. J. Dockray, Physiological Laboratory, University of Liverpool, Liverpool L69 3BX.Received for publication 16 May 1979 gastrinomas and hog antral mucosa Tracy, 1964, 1972). G34 and G17 may be sulphated or unsulphated at the tyrosine residue, which is in the sixth amino-acid position counting unconventionally from the carboxyl-terminus. Other circulating forms of gastrin have been described (big, big gastrin, component I, minigastrin, etc.) but these either do not increase after feeding or occur only in low concentrations and are unlikely to make more than a minor contribution to circulating gastrin biological activity (Stadil et al., 1975). Walsh and co-workers (1976) have studied the actions of G17 and G34 on gastric acid secretion in patients with duodenal ulcer and have shown that circulating G17 is six to eight times more potent than G34 in stimulating acid secretion. A relatively minor increase in the ratio of G17 to G34 could therefore ...