Endocrine tumors are distributed throughout the pancreas and can usually be removed by local excision or distal pancreatectomy. Those tumors arising in the pancreatic head and uncinate process may be difficult to enucleate because of size, location or malignant extension. In the past, surgeons have been reluctant to perform a pancreaticoduodenectomy (Whipple procedure) for these lesions because of the high morbidity and mortality rates. In recent years, we and others have reported a marked reduction in the morbidity and mortality rates after the Whipple procedure and, since 1981, have used pancreaticoduodenectomy to resect pancreatic endocrine neoplasms successfully in 12 patients. Tumors were resected from six men and six women who ranged in age from 28 to 61 years (median of 49 years). Six of the tumors were benign and included three insulinomas, one glucagonoma, one gastrinoma and one nonfunctioning islet cell tumor. The six malignant tumors included two insulinomas, one VIPoma and three nonfunctioning islet cell tumors. In all instances, enucleation could not be performed safely or would have resulted in an inadequate excision. Pylorus preservation was used in seven of the patients, including the last six. The average operative time was 6.8 hours, and six of the patients did not require perioperative blood transfusions. There was no hospital mortality. Hospital morbidity included three self-limited pancreatic fistulas, one gastrocutaneous fistula, one hepatic abscess and one postoperative myocardial infarction. One patient with a malignant VIPoma died three years postoperatively of metastatic tumor. The remaining 11 patients are alive and well with a median follow-up period of three and one-half years (range of zero to 9.7 years). These data indicate that pancreaticoduodenectomy is an appropriate procedure for properly selected patients with pancreatic endocrine neoplasms and can be performed with acceptable morbidity and mortality rates.