Methods: Eleven patients with sustained PEI and regular enzyme substitution were investigated at hospital, after a washout period without enzyme substitution, and later after reintroduction of substitution. The digestibility and postprandial metabolism of dietary protein were characterized after the ingestion of a semi-synthetic single meal containing 20 g (15)N-labeled casein. Results: At baseline, 20 +/- 8% of dietary nitrogen was transferred to the metabolic pools vs. 24.5 +/- 7% under enzyme treatment (P = 0.04). After treatment, the transfer of dietary nitrogen tended to increase in plasma amino acids, and increased significantly in plasma proteins and the deamination pool. In contrast, the fecal excretion of dietary nitrogen did not demonstrate any treatment effect. In patients not receiving insulin for diabetes, the treatment stimulated insulin secretion. Conclusions: Protein malabsorption was mostly undetectable using standard fecal tests. The study of the postprandial fate of dietary protein revealed a moderate increase of its transfer to metabolic pools after enzyme substitution.