Intraoperative radiation therapy has been introduced to improve survival rates after resection of biliopancreatic cancer. Early and late effects of intraoperative radiation on the exocrine and endocrine functions of the residual pancreas were examined in 54 patients with pancreatic head resection. Of the 54 patients, 20 underwent intraoperative radiation (A group) and the other 34 did not (B group). Fasting blood sugar level, a 120-min value of the 75-g oral glucose tolerance test, N-benzol-L-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion value (a pancreatic exocrine function test), and amount of postoperative pancreatic juice drainage were compared between groups A and B at preoperative and early and late postoperative times. Fasting blood sugar level and a 120-min value of the 75-g oral glucose tolerance test (OGTT) showed no change at the early (<2 months) postoperative period of the two groups. At the late (>6 months) postoperative period, fasting blood sugar showed no alteration, while the 75-g OGTT 120-min value increased compared to the preoperative level in both groups. In the group A, the 75-g OGTT 120-min value at the late postoperative period was significantly higher than those at the preoperative and early postoperative periods (289.4 +/- 104.9 vs 193.0 +/- 58.2 mg/dl, P = 0.0198 and 289.4 +/- 104.9 vs 184.4 +/- 104.9 mg/dl, P = 0.0285). Preoperative BT-PABA excretion value was not different between the two groups. It decreased at the early postoperative period and returned to the preoperative level at the late postoperative period in both the groups. The decline of BT-PABA in group A was 23 +/- 21%, which was significantly larger than 11 +/- 24% in group B. The total amount of postoperative pancreatic juice drainage from postoperative days (POD) 4-13 in group A was about half as much as that in group B (720.8 +/- 916.4 vs 1433.8 +/- 962.1 ml, P = 0.0128). Univariate and multivariate regression analysis of factors concerning the decline of BT-PABA values at the early postoperative period showed that intraoperative radiation was a significant independent determinant. In conclusion, these results suggest that intraoperative radiation causes significant deterioration of pancreatic exocrine function at the early postoperative period. Intraoperative radiation for resectable periampullary carcinoma should be reappraised based on the decline of the pancreatic exocrine function as well as the improvement of the survival curve.