Blood isotone contrast media is considered to be less toxic to vascular and pancreatic duct endothelium than high-osmolar contrast media. In this study we assessed the impact of a low-osmolar contrast agent compared with a blood isotone product on pancreatic damage induced by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic retrograde sphincterotomy (EST). In a prospective trial 42 consecutive ERCP/EST patients were randomized to receive either iopromid, a low-osmolar non-ionic contrast agent (770 mosmol/kg H2O), or iotrolan, a blood-isotone non-ionic product (320 mosmol/kg H2O). The endoscopies were performed by two experienced endoscopists. Forty patients were included in the study. Blood samples were collected before and 40 min, 2, 4, 6 and 24 h after the endoscopic procedure. Samples were analysed for pancreatic serum enzymes, acute-phase proteins and blood counts. A clinical pain score was investigated. Post-ERCP pancreatitis was diagnosed in 2 patients in the iopromid group and in 5 patients in the iotrolan group. There was no significant difference between groups in the time course of pancreatic serum enzymes, acute-phase proteins or in the pain score. Due to the small number of patients in this study, only stronger differences caused by the two contrast media could have led to statistically significant results. We did not observe statistically significant differences in comparing iotrolan and iopromid concerning ERCP/EST-induced pancreatic damage.