Macromolecules are known to precipitate selectively in concentrated solutions of polyethylene glycol. This report describes the use of polyethylene glycol 6000 to distinguish macroamylase from normalsized serum amylase. Preliminary studies indicated that a PEG concentration of 12% and a 10-min incubation at 37°C separated normal serum amylase from macroamylase. Using these conditions, study of 18 macroamylase-containing sera showed precipitation of at least 73% of the amylase activity. In contrast, in 46 normal sera and 16 hyperamylasemic (but not macroamylasemic) sera, <52% of the amylase activity was precipitated by polyethylene glycol. This test provides a rapid, simple, and accurate means of determining i f macroamylasemia is the cause of hyperamylasemia.