Islet tissue was prepared by collagenase ductal perfusion in mongrel dogs and transplanted to the spleen as autografts following total pancreatectomy. The graft was introduced into the spleen by reflux through tributaries of the splenic vein. Total insulin output by the in situ islet cell mass and by the heterotopically transplanted islet cell mass was studied by measuring insulin in the portal vein prior to pancreatectomy and two weeks after grafting. Basal insulin as well as the insulin output in response to 0.5 gram per kilogram of intravenous glucose were measured. Normoglycemia was achieved immediately in all grafted dogs. The results of intravenous glucose tolerance testing suggested only a mild degree of carbohydrate intolerance in the grafted dogs. Insulin output in 60 minutes after glucose stimilation was similar for in situ and grafted islet cells. The results of glucose clamp studies did not reveal any significant change in the insulin sensitivity of grafted as opposed to normal dogs. Islets of Langerhans may be harvested by the ductal perfusion method to yield a completely adequate islet cell mass for grafting purposes in the canine model following total pancreatectomy.