Immunoreactive glucagon (IRG) response to a 3 min iv infusion of 25 g glucose was examined in 7 nondiabetic Caucasians, 8 nondiabetic, 8 prediabetic and 16 diabetic Pima Indians to define the normal IRG response and to determine if abnormalities of IRG suppression occur in diabetic and prediabetic Pima Indians. Fasting IRG levels were similar in the 3 nondiabetic groups. In response to the glucose infusion the maximum percentage fall in plasma IRG concentration was similar in the normal Caucasians (37±4%) and the normal (42±2%) and prediabetic Indians (43±3%). In the diabetic Indians the relative fall was less at all sampling times than among the prediabetic or normal Indians. No evidence of any differences in IRG suppression in prediabetic and normal Indians or normal Caucasians was found. Without detectable change in insulin levels during the first 10 min following the glucose infusion, IRG levels in the diabetics fell but to a lesser degree than that in the other groups.