It has long been recognized that diabetes mellitus is characterized by alterations in amino acid metabolism. Our aim was to evaluate the fasting amino acid concentrations in insulin-dependent diabetic subjects treated with different kinds of insulin therapy and with respect to the resulting different metabolic control. Four groups of patients were studied: Group 1: eight type 1 diabetic patients with two daily insulin injections; Group 2: eight type 1 diabetic patients with continuous subcutaneous insulin infusion; Group 3: five type 1 diabetic patients with continuous intraperitoneal insulin infusion; Group 4: six patients with total pancreatectomy. In all patients fasting amino acid profile was determined. Group 1 was also studied after 24 hr insulin withdrawal and after acute normalization of glycaemia. Our data demonstrated that the patients with a mild hyperglycaemia showed a significant increase in plasma amino acid levels. The continuous subcutaneous or intraperitoneal insulin infusion normalized amino acid profile at the expense of peripheral hyperinsulinemia, suggesting the presence of insulin resistance with regard of amino acid metabolism. The acute normoglycaemia demonstrated that plasma branched chain amino acid levels are more sensitive than plasma glucose to insulin action. Moreover, the amino acid pattern of euglycaemic total pancreatectomized patients suggested that a basal level of glucagon is essential in regulating glycogenic amino acid plasma concentrations.