Patients with diabetes due to pancreatectomy have metabolic features different from Type 1 (insulin-dependent) diabetes after insulin withdrawal. Whether or not glucagon by itself or combined glucagon-insulin absence are responsible for this metabolic behaviour is unknown. This study was carried out to evaluate the ability of insulin replacement to abolish differences between patients with Type 1 diabetes and patients with diabetes due to pancreatectomy. We studied the diurnal patterns of intermediary metabolites, free insulin, and glucagon using the Biostator (glucose-controlled insulin infusion system) and intensive subcutaneous insulin therapy in five patients after total pancreatectomy, five after partial pancreatectomy and seven patients with Type 1 diabetes. All were studied for 24 h after an overnight period of normoglycaemia. Insulin requirement was lower in the patients with total pancreatectomy than in patients with partial pancreatectomy or Type 1 diabetes during both types of insulin treatment (p less than 0.05). Blood glucose and free insulin were similar in all the groups in both conditions. Immunoreactive glucagon was higher in the patients with diabetes secondary to pancreatectomy than in Type 1 diabetic patients. However, glucagon levels did not increase after arginine infusion in the patients with total pancreatectomy, and column chromatography of blood samples from two totally pancreatectomized patients showed no significant levels of immunoreactive pancreatic glucagon. Non-esterified fatty acids and ketone bodies were similar during Biostator and intensive subcutaneous insulin therapy. By contrast, gluconeogenic precursors (lactate, pyruvate, alanine and glycerol) were higher in patients with total pancreatectomy than in patients with partial pancreatectomy and Type 1 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)