Tissue polypeptide antigen (TPA) is a protein produced by rapidly growing tissues, such as placenta and neoplasms (Bj6rklund et al., 1976; Bjorklund, 1978). Increased serum levels of this antigen have been observed in a variety of malignant diseases of different origin: i.e. lung, breast, stomach and colorectal cancer (MenendezBotet et al., 1978; Schlegel et al., 1981). They have also been detected in several acute and chronic inflammatory conditions, especially liver cirrhosis and acute hepatitis (Bj6rklund, 1980). Only the occasional report appears in the literature on TPA measurements in pancreatic cancer (Andriulli et al., 1983). Moreover few data are available on the utility of serum TPA assay in the differential diagnosis between pancreatic cancer and chronic pancreatitis (Panucci et al., 1984). The aim of the present investigation was to evaluate the role of TPA in detecting pancreatic malignancy and its value in distinguishing pancreatic cancer from other pancreatic and benign extra-pancreatic gastrointestinal conditions. A total of 106 subjects were studied: 29 control subjects (19 male, 10 female, age range, 37-66 years) who were healthy members of the medical staff and blood donors; 28 with pancreatic cancer of duct cell origin (Cubilla & Fitzgerald, 1978) (20 male, 8 female, aged 43-71) always histologically confirmed; staging was: T,NoMo (3), T2N1Mo (6), T2N1M, (9), T3AM, (10); 24 with chronic pancreatitis (22 male, 2 female, aged 26-64) (7 with calcified chronic pancreatitis) diagnosed on the basis of the following examinations: abdominal x-ray for pancreatic calcifications, pancreatic ultrasonography, endoscopic retrograde pancreatography, CAT scanning. The diagnosis of chronic pancreatitis was always histologically confirmed on surgical biopsies. Twenty five were affected by gastrointestinal extra-pancreatic diseases of a nonmalignant nature (11 male, 14 female, aged 37-81): liver cirrhosis (6 cases), primary biliary cirrhosis (1), gallstones (4), common duct stones (3), benign stenosis of the papilla of Vater (2), chronic gastritis (4), duodenal ulcer (3), irritable colon (2). Diagnosis was made on the basis of the clinical picture and on the results of specific radiological and histological procedures. Serum TPA determination was performed by an RIA procedure (Prolifigen RIA kit, AB Sangtec Medical, Bromma, Sweden). The intra-assay (no = 15, mean= 125.5, s.d. =6.2 UI-) and interassay (no =7, mean= 122.6, s.d. = 12.3 U -1) coefficients of variation were 4.9% and 10.0% respectively. Serum specimens were always frozen at -20°C immediately after collection, and the