It is appropriate that glucagon should be the subject of a Banting Memorial Lecture, in that Banting and Best were probably the first to observe the biologic action of glucagon. In a letter written in 1971 to Dr. Piero Foa, long a leader in the glucagon field, Dr. Best reminisced about the historic 1921 experiments in which crude pancreatic extracts were injected into depancreatized dogs. 1 He wrote," I have a very clear recollection of the immediate rise in blood sugar to about 5 to 10 mg.%. This lasted about Vi hour. As you may know, we thought this might have been due to epinephrine liberation and, for this reason, we failed to investigate it thoroughly." An explanation for their oversight is not necessary. At that historic moment in medical history, they could hardly have been expected to concern themselves with the initial upward deflection of the blood sugar curve when their goal, the discovery of insulin, was in clear view. However, one year later, Murlin and Kimball reported that aqueous extracts of pancreas raised blood sugar levels of depancreatized dogs by 200 mg./lOO ml. or more. 2 They believed that this was due to a glucoregulatory hormone they named" glucagon," meaning" glucose-driving." But, for most of the half century since its discovery, glucagon was regarded either as a hormone of trivial importance or as a" nonhormone," an artifact of the extraction procedure for insulin. The possibility that it might play a role in human disease was not considered seriously. Ferner was one of the few who believed that glucagon was pathogenically involved in the metabolic derangements of diabetes mellitus, and he even proposed that the diabetes caused by total pancreatectomy was the result of gastrointestinal