SummaryPlasma immunoreactive cationic trypsin(ogen) levels were determined in 32 control subjects and 43 patients with varying degrees of pancreatic insufficiency including 35 with cystic fibrosis (CF) and eight with Shwachman's syndrome. In six CF infants less than 2 years of age, plasma trypsin(ogen) levels were significantly elevated (97.3 ± 62.2 ng/ml) above the normal range for nine controls (7.0 ± 5.9 ng/ml;P< 0.025). Four of these infants had steatorrhea, three of whom had undetectable duodenal trypsin activity after stimulation with secretin-cholecystokinin. In two CF infants, molecular size fractionation by gel filtration of plasma followed by radioimmunoassay of the column fractions demonstrated that trypsinogen was the only immunoreactive species in the circulation.In contrast, in older CF patients with steatorrhea (mean age, 15.3 ± 4.6 years), plasma cationic trypsin(ogen) levels were undetectable or low (1.1 ± 1.7 ng/ml). This finding clearly distinguished them from older CF patients without steatorrhea (mean age, 14.3 ± 3.9 years) in whom cationic trypsin(ogen) levels were significantly higher (23.3 ± 17.6 ng/ml;P< 0.01). The mean trypsin(ogen) concentration in the older CF patients without steatorrhea did not differ from the mean value for 23 normal subjects of similar age. Plasma cationic trypsin(ogen) levels in two Shwachman's patients with steatorrhea (0.19 and 0.86 ng/ml) were significantly lower than the values found in six Shwachman's patients without steatorrhea (5.9 ± 2.3 ng/ml;P< 0.025). Furthermore, in nine older CF patients and eight Shwachman's patients, circulating trypsin(ogen) levels were highly correlated with duodenal trypsin output after secretin-cholecystokinin stimulation (r = 0.946,P< 0.01; r = 0.899,P< 0.01, respectively). These results suggest that in CF infants high levels of circulating trypsin(ogen) persist even in those with complete pancreatic insufficiency. In older CF patients and those with Shwachman's syndrome, however, circulating trypsin(ogen) accurately reflects residual pancreatic function.SpeculationCystic fibrosis (CF) infants often possess viable but ductally obstructed pancreatic tissue, which may be destroyed with disease progression. The correlation between pancreatic exocrine function and circulating trypsin(ogen) in older CF patients and Shwachman's patients, however, indicates that ductal obstruction is not a prominent feature in these patients.