Serum levels of SPan-1 were determined in patients with various gastrointestinal cancers including pancreatic cancer and benign disorders, as well as from healthy subjects, by using a newly developed SPan-1 antigen immunoradiometric assay (SPan-1 RIABEAD, Dainabott). In addition, usefulness of diagnosis for pancreatic cancer by determination of Serum SPan-1 antigen was compared with that of other tumor markers such as CA 19-9, DU-PAN 2, CA 50, CEA and elastase 1 in the same patients. Serum SPan-1 antigen levels in healthy controls ranged from 0 to 156 U/ml with a mean of 7.7 U/ml (+/- 15.0, 2 S.D). Thirty U/ml of serum SPan-1 antigen levels was set as the cut-off value, and 98.9% of healthy controls were within this cut-off value (30 U/ml). Serum SPan-1 antigen levels in pancreatic cancer were distributed from 0-353, 900 U/ml with a mean of 14,466 U/ml (+/- 16.616 SD). Sensitivity of SPan-1 antigen in pancreatic cancer was 81.9%, which was the highest among gastrointestinal cancers, and eight of nine pancreatic cancer patients with stage II showed above normal limits (30 U/ml). Although serum SPan-1 antigen levels in biliary tract cancer and liver cirrhosis showed a high percentage (70.3%, 56.8%), the mean values of SPan-1 antigen levels in these groups were 477 U/ml and 62.8 U/ml, respectively, which was lower than that of pancreatic cancer. False positive ratio of SPan-1 antigen in benign pancreatic disease was lower than that of CA 19-9. Also, comparative studies of SPan-1 antigen and various tumor markers between pancreatic cancer and benign gastrointestinal diseases revealed that SPan-1 antigen showed the highest sensitivity and accuracy in diagnosis for pancreatic cancer among other tumor markers. From these results, measurement of SPan-1 antigen appeared to be the most useful marker in the diagnosis of pancreatic cancer.