Hydrocortisone treatment increased blood glucose and plasma insulin levels in adrenalectomized rats. Insulin secretion during the immediate secretory response as well as the late phase of glucose-induced insulin release from the perfused pancreas from adrenalectomized rats was three times higher after hydrocortisone treatment. Glucose inhibited glucagon secretion from the perfused pancreas of adrenalectomized rats after hydrocortisone treatment but not from the pancreas of untreated animals. The immediate insulin secretory response to tolbutamide was increased by hydrocortisone treatment whereas tolbutamide did not affect glucagon release from the perfused pancreas of adrenalectomized hydrocortisone treated rats or control animals.