The effect of fasting on serum and antral gastrin concentrations and G cell ultrastructure in the rat has been examined using a radioimmunoassay and quantitative electron microscopy. Serum gastrin levels in fasting animals were markedly reduced and there was also a significant decrease in antral gastrin concentrations after 48 hours and 72 hours of fasting. This was associated with a significant fall in the granule content and cytloplasmic volume of individual G cells, at its greatest by 48 hours. A relative absence of electron dense granules in the Golgi zones of cells from animals fasted for 72 hours suggested a paucity of newly formed granules, but fasting produced no detectable change in the electron density of the granule population taken as a whole. The results indicate that, during fasting, release and then synthesis of gastrin is inhibited, so that granule stores and cell size diminish. The correlation between the granule content of G cells and the antral content of gastrin suggests that hormone release occurs by exocytosis, rather than by any change in the content of individual granules.