Background and Study Aims: Hyperamylasaemia occurs in up to 60% of patients following endoscopic retrograde cholangiopancreatography (ERCP), and in a small proportion of patients (1-5%) acute pancreatitis may develop. We evaluated the role of the neutrophil in post-ERCP hyperamylasaemia and acute pancreatitis by measuring circulating CD11b adhesion receptor expression - an indicator of leukocyte activation. Patients and Methods: A total of 43 patients undergoing elective ERCP were studied. Peripheral blood measurements of amylase activity and neutrophil CD11b content (by flow cytometry) were made immediately before ERCP (baseline), and at 2 and 24 hours after the procedure, Results: ERCP induced an increase in amylase level above baseline in 41 of 43 patients, The 2-hour and 24-hour post-ERCP amylase levels were directly related (R = 0.9, P < 0.01), Baseline CD11b receptor status was positively correlated with post-ERCP amylase activity (R = 0.4, P < 0.05), and this relationship was stronger when pancreatography had been performed (R = 0.67, P < 0.01), Three patients (7%) developed clinical acute pancreatitis, with post-ERCP amylase levels persistently elevated above 1000IU/l, Multiple linear regression identified CD11b expression as the most significant explanatory variable for amylase level after ERCP (multiple R = 0.74, P < 0.01). Conclusions: The findings from this pilot study indicate an association between neutrophil activation and hyperamylasaemia following ERCP, and suggest a role for this leukocyte in the pathogenesis of pancreatitis. Further study of neutrophil characteristics may allow identification of individual susceptibility to ERCP-induced pancreatic injury.