To compare the effect on glucose recovery after insulin-induced hypoglycaemia of intramuscular genetically engineered glucagon, intramuscular glucagon from pancreatic extraction and intravenous glucose, we examined 10 healthy subjects during blockage of glucose counterregulation with somatostatin, propranolol and phentolamine. Each subject was studied on three separate occasions. Thirty min after a bolus injection of 0.075 iu soluble insulin per kilogram body weight the subjects received one of the following treatments: 1 mg glucagon from pancreatic extraction intramuscularly; 1 mg genetically engineered glucagon intramuscularly; and 25 g glucose intravenously, respectively. The two glucagon preparations induced an equally rapid increase in plasma glucose. This was due to an abrupt (within 4 min) and equal increase in glucose appearance rate. The increases in both plasma glucose and in glucose appearance rate were far more protracted after i.m. glucagon than after i.v. glucose. These results suggest that genetically engineered glucagon and glucagon from pancreatic extraction have a similar effect on hepatic glucose production rate. Due to the protracted effect of intramuscular glucagon, a combined treatment consisting of both intravenous glucose and intramuscular glucagon may be more effective in the treatment of hypoglycaemia than any of these given alone.