The indications and outcomes of aggressive reoperation in patients referred to the National Cancer Institute (NCI) for protocol therapy of locally advanced pancreatic carcinoma were investigated. Twenty-nine patients referred to the NCI after exploration and determination of unresectability elsewhere were considered to have localized disease after a metastatic work-up. These patients were then entered onto NCI adjuvant therapy protocols and taken to exploratory laparotomy. Intraoperatively, patients underwent complete resection if possible; otherwise varying palliative surgical procedures were performed. Of the 29 patients, 16 underwent complete resection of their disease, and 13 were unresectable. Two patients suffered postoperative mortality. Disease-specific survival of the resected patients was significantly better than that of the unresectable patients (P < 0.01). The two long-term survivors (53 and > 109 months) underwent definitive surgery after a palliative procedure elsewhere. Complete resection of pancreatic carcinoma contributes to increased survival. The intraoperative definition of unresectability in pancreatic cancer varies with the degree of pancreatitis present, the surgical expertise of the surgeon, and the available ancillary services. Given the extremely grave prognosis of patients with unresectable pancreatic carcinoma, locally unresectable patients without peritoneal seeding or distant metastases at exploration should be considered for referral for protocol therapy to centers where expertise in radical surgery for pancreatic cancer exists. 0 1996 Wiley-Liss, hc.*