The increased incidence of severe hypoglycemia reported in young children with diabetes is consistent with a defect in glucagon secretion or a generalized abnormality in islet hormone secretion. To assess pancreatic hormone and gastric inhibitory polypeptide secretion in children with early onset diabetes, 12 children with onset of diabetes prior to the age of 28 months were studied and the data compared to the hormone responses observed in 11 children with LOD, diagnosed after the age of 5 years. Plasma glucose, C-peptide, glucagon, pancreatic polypeptide, and gastric inhibitory peptide concentrations were measured during and following an arginine infusion (500 mg/kg over 60 minutes) and a mixed meal. During arginine infusion, plasma glucose and glucagon increased similarly in both groups and returned to basal concentrations following discontinuation of arginine infusion. In contrast, plasma C-peptide, hPP, and GIP concentrations did not change. Following the mixed meal plasma glucose, hPP, and GIP concentrations increased similarly in the two groups of children, but no change was observed in either plasma glucagon or C-peptide concentrations in either group. These data demonstrate that EOD and LOD are associated with insulin insufficiency alone and that abnormalities in secretion of other pancreatic islet hormone or GIP cannot be implicated in the high incidence of severe hypoglycemia observed in children with EOD.