In an attempt to assess the ethnic variability of diabetes mellitus, a comparative study of the clinical and metabolic features of diabetes in the Navajo Indian and Pennsylvania Amish was undertaken. The Navajo have a mild form of diabetes in which the juvenile ketotic form is unknown and complications are rare, while the Amish have both juvenile and maturity-onset forms with all of the acute and chronic complications. The mean peak plasma immunoreactive insulin (IRI) concentrations attained following oral ingestion of 100 gm of glucose differed significantly in the two groups of diabetics, suggesting that they may represent distinct disorders. There was more than a threefold difference in the maximal plasma IRI response between the normal Navajo and normal Amish, indicating that there is marked ethnic variability in the normal insulin response to an orally given glucose load.