To elucidate the impact of subcutaneous insulin infusion (CSII) treatment on the glucagon response to intravenous (IV) arginine and to oral glucose a 6-month prospective randomized study in insulin-dependent diabetics was carried out. The effects were investigated of CSII (7-patients) and conventional insulin treatment (UCT) (9 patients) on the changes in glucagon, growth hormone, glucose, lactate, glycerol, 3-hydroxybutyrate, and alanine to IV arginine and to oral glucose in insulin-dependent diabetics who were made euglycemic and isoinsulinemic using the artificial pancreas (Biostator, Miles, Elkhart, IN). HbA1c was significantly lower in the group treated by CSII. Despite the improved glycemic control no significant change in the responses of A-cell secretion to arginine or glucose challenges was found. In addition, there were no significant differences in hormone or metabolite values between the two groups at entry to the study or after 6 months of either therapy. Thus, normalization of the A-cell sensitivity to glucose in insulin-dependent diabetic subjects requires further amelioration of the intermediary metabolism than can be achieved with insulin pump treatment.