The development of a model of diabetes mellitus using swine offers the potential for new investigations in the study of human diabetic complications. In particular, animal models for the study of accelerated atherosclerosis associated with diabetes are important and presently lacking. Swine were selected because they have a natural susceptibility to atherosclerosis and have plasma lipoprotein patterns which are close to those of humans. Diabetes mellitus was induced in nine miniature swine by total pancreatectomy. Following surgery, they were maintained on porcine derived insulin at doses predicated on blood glucose levels. Pancreatic enzymes were replaced by dietary supplementation. Eight of the nine pigs were pancreatectomized successfully and stabilized with insulin. After initial weight loss, the pancreatectomized pigs maintained growth rates comparable to controls. Hypoglycemia and bacterial infections were the major problems experienced. Post-operative survival ranged from 50 days to 455 days. Our study shows that swine can be pancreatectomized successfully and maintained as insulin dependent animals, presenting a realistic model for research on the complications of diabetes.