Although it is known that caerulein exerts an action on the secretory activity of the islets of Langerhans in the pancreas, the mechanism of this hormone has not yet been ascertained. The present investigation was undertaken to observe the ultramicroscopic changes of the pancreatic islets and the peripheral blood levels of insulin, glucagon, glucose and electrolites after caerulein administration. The animals were divided into four groups, and three were injected intraperitoneally with caerulein at 25 micrograms/kg, 2 micrograms/kg and 0.2 microgram/kg body weight, respectively. The fourth group served as the control. In the first group (25 micrograms caerulein), the endocrine cells of the pancreatic islets showed accelerated functioning immediately and up to about 2 hours after injection. Then these cells degenerated due to cytoplasmic edema and evidenced decreased secretory activity. In the second group (2 micrograms) depression in the secretory activity occurred for about 2 hours immediately after the injection, but there was no destruction of cells and they gradually recovered their functioning. The third group (0.2 microgram) displayed an acceleration of secretory activity immediately after the injection and then recovered to the normal state. There were some changes of electrolites in the peripheral blood in each of the three groups, suggesting that caerulein causes acceleration and depression of the secretory activities in the islets of Langerhans in the pancreas depending on the dosage. Moreover, the cell alterations may well depend on the changes of electrolites in the inner and outer atmospheres of the cells.