Total plasma amino acids were determined by the ninhydrin method in 37 controls and 30 patients with chronic pancreatitis and normal (n = 7) pancreatic enzyme output or mildly (n = 6), moderately (n = 8), and severely (n = 9) reduced pancreatic enzyme output. Intravenous injection of synthetic secretin did not change plasma amino acid levels. During a combined intravenous infusion of secretin (1 CU/kg X h) and pancreozymin (1 Ivy dog unit/kg X h), amino acid concentrations decreased maximally by 31% +/- 19% (mean +/- SD) in controls, but only by 6.3% +/- 4.7% in patients with exocrine pancreatic insufficiency (p less than 0.001 vs. controls). At a cutoff limit of less than or equal to 12% for the decrease in total amino acids, mild exocrine insufficiency (20%-40% of mean normal chymotrypsin output) was identified with a sensitivity of 67%, whereas moderately to severely impaired function was detected in every case (overall sensitivity 91%). Pancreatic function, as assessed by duodenal intubation and the tubeless amino acid test, was significantly correlated (e.g., rs = 0.73 for chymotrypsin output, p much less than 0.001). In 15 controls and 13 patients with mildly (n = 5) to severely impaired pancreatic function, individual amino acids were estimated. Plasma serine kinetics completely distinguished both groups. Kinetics of serine, valine, isoleucine, and histidine correlated even better with pancreatic function than those of total amino acids.