Sera from patients with various malignant benign disorders, as well as from a large number of healthy blood donors (2197). were analyzed with a newly developed SPan-1 coated bead radioimmunoassay. Only 0.9% of the healthy patients had SPan-1 levels above the cut-off value. SPan-1 antigen levels were elevated in 89.2% of sera from pancreatic cancer patients and in 75% of T1 and T2 cancers. High diagnostic accuracy was also recognized in differentiating benign pancreatic diseases from pancreatic cancers. SPan-I levels decreased after pancreatic resection and rose again at recurrence of disease. SPan-1 could be distinguished from other tumor markers such as DU-PAN-2 and OC-125 by competition radioimmunoassays and was elevated in individuals with malignant gastrointestinal diseases who had normal levels of either or both CEA and CA 19-9 antigens. This rapid. reproducible and sensitive assay for SPan-I appears to be a useful procedure for the detection and follow-up of pancreatic cancer.