For 81 cases of resectable pancreatic carcinoma, the site of cancer origin, cancer histologic features, and hyperplasia in the noninvolved duct were studied in relation to diabetes. They were classified into the following three groups: (1) fasting blood sugar (FBS) of less than 120 mg/dl (Group A, 26 cases); (2) FBS of more than 120 mg/dl with less than 2-year history of diabetes (Group B, 38 cases); and (3) FBS of more than 120 mg/dl with more than a 2-year history of diabetes (Group C, 17 cases). Although neither tumor size nor tumor location differed between the three groups, both the highest resectability (47%) and the lowest rate (71%) of extrapancreatic invasion were seen in Group C. A pancreatic ductogram showed that the pattern of the main pancreatic duct was intact in 0% in Group C versus 35% in Group A (P less than 0.05). Histologically, papillary/well-differentiated adenocarcinoma was present in 35% of Group A patients versus 61% of Group B and 71% of Group C patients (P less than 0.05). Papillary hyperplasia was present in the ducts of 27% of the patients in Group A; this was significantly lower than the other two groups. Atypical duct hyperplasia was present in 47% of Group C patients; this was significantly higher than in the other two groups. It appears that cells in the main pancreatic duct are vulnerable to hyperplastic and well-differentiated cancerous changes in patients with a history of diabetes of more than 2 years duration.