I recently described a new form of pancreatic hyperenzymemia in healthy subjects in the absence of any pancreatic disease. The aim of this study was to determine whether this pancreatic hyperenzymemia has a familial distribution. From January 1996 to January 1999, 25 subjects with chronic nonpathological pancreatic hyperenzymemia were seen, in 23 of whom it was possible to investigate family members. A total of 102 subjects was studied. In addition to clinical history, physical examination and routine blood analysis, serum amylase, pancreatic isoamylase, lipase, and amylasuria were determined. Abdominal ultrasonography was also performed. Seven of the 23 families studied were found to have more than one member with pancreatic hyperenzymemia. In all, 19 persons (eight female and 11 male) were found to have this trait (mean age, 32.7 years; range, 3-84). The increase in enzyme concentration over the upper normal limit was in the range of 1.3- to 5.2-fold for amylase, 1.4- to 8.6-fold for pancreatic isoamylase, and 1.6- to 18.0-fold for lipase. Amylasuria was also increased. Clinically, no subject had symptoms or signs of pancreatic or other disease. Abdominal ultrasonography was normal in all of them. The results of this study show that pancreatic hyperenzymemia in healthy subjects may present with a familial distribution. The underlying defect in this disorder is not known. Although it is a benign condition, awareness of it is important to avoid unnecessary concern, examinations, and expenditure.