Carbohydrate metabolism was studied in 6 adult patients with phenylketonuria both on a low phenylalanine and an unrestricted institutional diet. Tolerance tests included PO glucose, PO phenylalanine, and combined glucose phenylalanine loading. Glucose, insulin, pyruvate, lactate, and phenylalanine were sampled at 0, 1/2, 1, 2, 3, and 4 hr. Fasting glucose levels were normal as were mean glucose values after challenge. Basal insulin secretion, as well as insulin response, to glucose challenge and to combined phenylalanine and glucose loading appeared normal. Insulin response to phenylalanine alone, however, was lower than expected in the phenylketonuria patients. Both off and on low phenylalanine diet, blood pyruvate and lactate were also normal. Thus, our data from blood did not show evidence of the abnormalities in glucose and pyruvate metabolism which have been proposed to occur in phenylketonuric patients but did not suggest that the potency of phenylalanine as an insulin secretagogue is diminished by chronic hyperphenylalaninemia.