The effect of peripheral and intraportal infusions on 0.86 pmol/kg-min-1 of glucagon on plasma glucose, plasma insulin, and glucose tolerance was examined in four normal subjects. Peripheral glucagon concentrations increased by 60--90 pmol/1 during intraportal and 70--180 pmol/1 during peripheral infusions. The infusions caused increases in plasma glucose levels of approximately 1 mmol/1, and in plasma insulin levels of 75--100%, regardless of route of administration. Intravenous glucose tolerance tests carried out during the glucagon infusions showed that glucose tolerance remained within the normal range and was uninfluenced by the route of administration.