It is of great importance to be able to distinguish hyperamylasemia linked to a pathological condition of the pancreas from one due to the presence of the macroamylase in the serum of the patient. We have evaluated both gel filtration chromatography and precipitation by PEG-6000 for the detection of serum macroamylase. Our study has enabled us to define a simple detection protocol, suitable for routine laboratory use. In this protocol, macroamylasemia is detected initially by precipitation with PEG-6000; if less than 60% of amylase activity is precipitated, there is no macroamylasemia. If more than 60% of amylase activity can be precipitated by PEG-6000, macroamylasemia is confirmed by gel filtration chromatography. The incidence of macroamylasemia in hospitalized patients was studied; it was 1.3% in cases where amylasemia was normal, and 4.5% in hyperamylasemic patients.