This is a retrospective review of 237 patients who had surgical exploration for proven or suspected malignant lesions of the pancreas (201 patients) and periampullary structures (36 patients). Among the former group, 128 patients had carcinoma diagnosed at initial operation (31 by resected specimens, 33 by liver, and 64 by other biopsies), four patients had Whipple resection for suspected carcinoma of pancreas but specimen showed chronic pancreatitis, and 69 patients had suspected carcinoma of the pancreas without histological proof. Among patients who had Whipple resections, the operative mortality was 20%. Over 40% of the deaths was due to systemic complications. Among patients with unresectable lesions, 19% died postoperatively. This figure correlated more with the condition of the host and the extent of the tumor rather than with the specific operative procedures: The operative mortality was 16-18% for those who had either biliary or duodenal bypass, 11% for those who had both type of bypass procedures, and 36% for those who did not have any bypass performed. Although near 60% of the death was secondary to advanced state of the malignant condition, some death could have been delayed or altered by more optimal biliary, duodenal decompression, and added therapy to decrease gastric acid. In patients with unresectable carcinoma of the head of the pancreas, the most optimal palliative procedures appear to be choledochojejunostomy constructed with a side-to-side anastomosis between common or hepatic bile duct and a loop of jejunum, supplemented with an enteroenterostomy below the biliary anastomosis, and a high gastrojejunostomy as a therapeutic or prophylactic treatment of duodenal obstruction.