Groups of subjects with different degrees of glucose intolerance were examined in order to determine, first, the capacity of the beta cells to release insulin upon glucose stimulation and, second, sensitivity to insulin. The groups were selected on the basis of fasting blood glucose value and tolerances to oral and intravenous glucose administration. The body weights, ages, and sexes of the subjects were well matched with those of control subjects with normal tolerances to oral and intravenous glucose administration. Computer analysis of the glucose and insulin curves during a standardized glucose infusion test made possible the measurement of the initiatory (parameters KI and IP) and potentiatory (parameter KP) effects of glucose on insulin release and of the sensitivity to endogenous insulin (parameter KG). In subjects with impaired oral but normal intravenous glucose tolerance tests, KG was decreased, KP was increased, and KI and IP were normal. However, in these subjects, KI and IP were considerably lower than in a matched group of control subjects with the same decrease in KG but with normal oral and intravenous glucose tolerance tets. In subjects in which both oral and intravenous glucose tolerance tests were impaired and in subjects with mild manifest diabetes, KI, IP, and KG were decreased whereas KP was normal. These data suggest that all stages of glucose intolerance are accompanied by a decreased ability of glucose to initiate insulin release and by decreased sensitivity to insulin. These derangements seem to be partially compensated for by enhancement of the capacity of glucose to potentiate insulin release in subjects with decreased oral but normal intravenous glucose tolerance tests.