The ultrastructural changes in pancreatic β cells were studied following glucose-induced insulin secretion in vitro, at two different extracellular pH (7.4 and 7.8). The pancreata perfused at pH 7.4 exhibited a biphasic insulin response to glucose challenge together with signs of increased emiocytotic activity and numerous microtubules in the β cells. Conversely, the pancreata perfused at pH 7.8 showed a significant decrease in insulin secretion, and their β cells revealed scarce emiocytotic images and a marked increase of intracellular granulolysis. These results represent the ultrastructural correlate of the reduced insulin secretion produced by metabolic alkalosis in the perfused rat pancreas.Centro de Endocrinología Experimental y Aplicada