We describe a very rare case in which macroamylasemia was associated with ulcerative colitis of total colitis type. The patient's serum amylase isozyme pattern by electrophoresis showed a broad abnormal peak toward the side of the positive pole compared with regular salivary and pancreatic fractions. Sephadex G-200 column chromatography showed a sedimentation coefficient of 6.6 S. Amylase activity was bound to IgG. Double diffusion experiments demonstrated that amylase activity could be precipitated in gel by an antibody to the lambda chain. Although inflammatory bowel disease is occasionally associated with hyperamylasemia due to pancreatitis, we emphasize that, when hyperamylasemia is recognized in patients with inflammatory bowel disease, macroamylasemia also should be considered.