Effects of irradiation on the pancreas was studied in 6 dogs receiving a dose equivalent to the biologic effect of 4000 R/6 weeks (with a nominal standard dose of 1175 rets) given to patients with Hodgkins disease. After control secretory, histologic and pancreatographic studies, 6 Thomas fistula dogs were subjected to 2400 R tumor dose over two weeks. There was a biphasic response to secretin alone or secretin with cholecystokininpancreozymin. An initial hypersecretion occurred at 2 weeks—volume was increased, but bicarbonate and enzyme output remained unchanged. Thereafter there was a progressive reduction in volume, bicarbonate and enzyme outputs (>90% after 3 months). Histology showed early ductal reduplication but with progressive fibrosis, features compatible with chronic pancreatitis. Pancreatic insufficiency may contribute to post-irradiation gastrointestinal symptomatology. Close field irradiation of the pancreas results in actual destruction of the parenchyma.