The observations that the peptide hormone gastrin interacts with transferrin in vitro, and that circulating gastrin concentrations are increased in the iron loading disorder haemochromatosis, suggest a possible link between gastrin and iron homeostasis. This study tested the hypothesis that gastrin and iron status are interrelated, by measurement of iron homeostasis in mice and humans with abnormal circulating gastrin concentrations. Intestinal iron absorption was determined by ⁵⁹Fe uptake following oral gavage, and concentrations of duodenal DMT-1 and hepatic hepcidin mRNAs by quantitative real-time PCR, in agastrinemic (GasKO), hypergastrinemic cholecystokinin2 receptor-deficient (CCK2RKO), or wild-type mice. Iron status was measured by standard methods in the same mice, and in hypergastrinemic humans with multiple endocrine neoplasia type 1. Iron absorption was increased 6-fold and DMT-1 mRNA concentration 4-fold, and transferrin saturation was reduced 0.8-fold and hepcidin mRNA expression 0.5-fold, in juvenile GasKO mice compared to age-matched wild-type mice. In mature mice few difference were observed between the strains. Juvenile CCK2RKO mice were hypergastrinemic and had a 5.4-fold higher DMT-1 mRNA concentration than wild-type mice, without any increase in iron absorption. In contrast to juvenile GasKO mice, juvenile CCK2RKO mice had a 1.5-fold greater transferrin saturation which was reflected in a 2-fold increase in liver iron deposition at maturity compared to wild-type mice. The correlation between transferrin saturation and circulating gastrin concentration observed in mutant mice was also observed in human patients with multiple endocrine neoplasia, in whom hypergastrinemia correlated positively (p = 0.004) with an increased transferrin saturation. Our data indicate that, in juvenile animals when iron demand is high, circulating gastrin concentrations may alter iron status by a CCK2R-independent mechanism.