SummaryAltered exocrine gland function is characteristic of cystic fibrosis (CF). This study was undertaken to determine the relationship between pancreatic and salivary exocrine dysfunction in CF. We have measured serum pancreatic (P) and salivary-like (S) isoenzyme concentrations in CF patients, their obligate heterozygote parents and normal controls (N) using a quantitative gel-electrophoretic method. Our results show that serum levels of these isoenzymes correlate with the respective pancreatic and salivary gland amylase output and, therefore, can be used as measures of pancreatic and salivary exocrine function. Thus, P isoenzyme levels are low in CF patients with pancreatic insufficiency (mean ± S.D.: 1.3 + 0.6 starch units per liter versus 5.8 ± 1.7 for the N group,P< 0.001). In contrast, P isoenzyme levels are elevated in CF patients with adequate pancreatic function (12.0 ± 5.3;P< 0.002 versus N). Whereas P isoenzyme levels differentiate CF patients with pancreatic insufficiency from those with adequate pancreatic function, S isoenzyme levels are equally elevated irrespective of pancreatic function (12.5 ± 5.3 and 12.5 ± 5.2versus8.1 ± 2.7 for the N group,P< 0.001 and < 0.01, respectively). Thus, increased salivary amylase levels in CF patients are not due to a compensatory mechanism for reduced pancreatic amylase output, but rather are intrinsic to CF. In those patients with adequate pancreatic function, the increased S isoenzyme levels correlate with increased P levels (r= 0.72), indicating defective control of both pancreatic and salivary exocrine secretion in CF. In obligate heterozygote samples, P isoenzyme levels are increased (7.6 ± 2.5;P< 0.05 versus N) whereas S isoenzyme levels are normal (8.2 ± 5.6), indicating that this defect is partially expressed in the carrier state. We conclude that elevated saliva amylase and altered serum amylase isoenzyme levels in the CF patient and carrier state are due to a generalized defect in exocrine gland secretory regulation in CF.SpeculationWe speculate that the altered exocrine secretion in cystic fibrosis patients and their parents is due to the presence of an extra, cystic-fibrosis-associated, stimulatory agent and that the exocrine pancreas is more sensitive to this agent than are the salivary glands.