Pure pancreatic fluid was aspirated at the time of endoscopic retrograde cholangiopanereatography (ERCP), after Secretin stimulation, and was analyzed for protein in eight patients with proven adenocarcinoma of the pancreas and in 16 subjects of the same sex ratio and approximately matching ages, who had normal pancreatograms and pancreatic cytology, who served as controls. The albumin concentration, IgA, IgG, were all significantly greater in the pancreatic fluid of the cancer group, and the IgM and transferrin increase was of borderline significance. Many zymogen bands present in controls were either faintly present or absent in the cancer group at matching zymogen concentration. Cytology was positive or suspicious in eight of 11 cancer patients. The secretory protein abnormalities and cytology results in the cancer group did not depend on a particular tumor site or size, the smallest being 3 cm lesions. Hence, secretory abnormalities and gross tumor size and location are independent entities to a certain extent. It is possible that secretion changes may precede the development of gross tumor. Further study will be necessary before the actual significance of these findings for early diagnosis is known.