Due to the existence of isotope effects on some metabolic pathways of amino acid and protein metabolism, animal tissues are N-15-enriched relative to their dietary nitrogen sources and this N-15 enrichment varies among different tissues and metabolic pools. The magnitude of the tissue-to-diet discrimination (Delta N-15) has also been shown to depend on dietary factors. Since dietary protein sources affect amino acid and protein metabolism, we hypothesized that they would impact this discrimination factor, with selective effects at the tissue level. To test this hypothesis, we investigated in rats the influence of a milk or soy protein-based diet on Delta N-15 in various nitrogen fractions (urea, protein and non-protein fractions) of blood and tissues, focusing on visceral tissues. Regardless of the diet, the different protein fractions of blood and tissues were generally N-15-enriched relative to their non-protein fraction and to the diet (Delta N-15. 0), with large variations in the Delta N-15 between tissue proteins. Delta N-15 values were markedly lower in tissue proteins of rats fed milk proteins compared to those fed soy proteins, in all sampled tissues except in the intestine, and the amplitude of Delta N-15 differences between diets differed between tissues. Both between-tissue and between-diet Delta N-15 differences are probably related to modulations of the relative orientation of dietary and endogenous amino acids in the different metabolic pathways. More specifically, the smaller Delta N-15 values observed in tissue proteins with milk than soy dietary protein may be due to a slightly more direct channeling of dietary amino acids for tissue protein renewal and to a lower recycling of amino acids through fractionating pathways. In conclusion, the present data indicate that natural Delta N-15 of tissue are sensitive markers of the specific subtle regional modifications of the protein and amino acid metabolism induced by the protein dietary source.