Background: Microlithiasis has been implicated in the etiology of idiopathic pancreatitis and biliary-type pain in patients with intact gallbladders. Contrast injection at endoscopic retrograde cholangiopancreatography (ERCP) is used to confirm access into the bile duct and bile is also aspirated to look for microlithiasis. It is not known whether contrast agents contain crystals that could mimic true microlithiasis. Methods: Four mL of 2 contrast agents (Hypaque and Omnipaque) were examined after centrifugation under polarizing microscopy. In the second part of the study, bile aspirated during ERCP with contrast injection was examined for microlithiasis and contrast pseudomicrolithiasis. Results: Contrast agents exhibited pseudomicrolithiasis that mimicked calcium bilirubinate granules. Pathologists participating in the study were not aware of contrast pseudomicrolithiasis. Nine of twelve (75%) patients would have been reported as having microlithiasis and would possibly have undergone an unnecessary cholecystectomy. Conclusion: When bile collected during ERCP is to be examined for microlithiasis, it should be collected without contamination by a contrast agent. If this is not possible, pathologists should be aware that contrast can cause pseudomicrolithiasis. (Gastrointest Endosc 2000;51:401-4.)