The proposition that glucagon plays an essential part in maintaining hyperglycæmia in diabetes has been investigated by the study of 5 totally pancreatectomised subjects and 5 age and sex matched insulin-dependent diabetic patients. True basal glucagon values were obtained by the use of a new affinity chromatography technique. The mean fasting plasma-glucose levels of the pancreatectomised subjects was 251±46 mg/dl. The mean fasting plasma-glucagon level was not significantly elevated above zero (13±0·6 pmol/l) and showed no change following arginine. In the 5 insulin-dependent diabetics the mean fasting plasma-glucagon level of 17·2±5·3 pmol/l rose to a maximum at 25 minutes of 103·6±27·5 pmol/l during infusion of arginine. These findings imply the absence of a significant number of normally functioning alpha cells in extrapancreatic sites in man and demonstrate that pronounced hyperglycæmia may occur in the absence of glucagon. Glucagon is probably not of primary importance in the hyperglycæmia of insulin-dependent diabetics.