The apparent molecular weight of previously studied macroamylases is considerably larger than normal serum amylase, and the existence of macroamylase has therefore been easily documented by crude gel filtration techniques. This report describes a patient with a persistently elevated serum amylase level resulting from an unusual macroamylase which was only marginally larger than normal. The slightly increased size of this enzyme markedly influenced its renal clearance, and the existence of this macroamylase was first suspected because of the patient's consistently low C(Am) : C(Cr) ratio. Documentation of the increased size of this enzyme required careful gel filtration study. Isoelectric focusing showed this macroamylase to have a lower isoelectric point than did the two major components of normal serum amylase. The development of mild pancreatitis after pancreatic duct cannulation provided a unique opportunity to observe the serum and urine amylase values that occur when pancreatitis is superimposed on an underlying macroamylasemia.