Collagen is the most abundant extracellular matrix protein in animal tissues, and heat-denatured collagen (gelatin) and its hydrolysate (collagen peptide) are frequently used as food supplements. Clinical trials revealed that supplemental ingestion of 5-10 g collagen peptide daily improved the properties of facial skin, suppressed ultraviolet-induced skin erythema, and improved the T-cell-related immune status of Japanese people who ingest an average of 1.9 g collagen from their daily diet. Ingested collagen is digested and absorbed partly as prolylhydroxyproline (Pro-Hyp) and hydroxyprolylglycine (Hyp-Gly), resulting in their rather high concentrations in blood. The beneficial effects of collagen peptide ingestion appear to be mediated at least partly by these collagenderived dipeptides. Collagen-derived Pro-Hyp exhibits physiological activity in the in vitro differentiation processes of skin fibroblasts, chondrocytic cells, and pre-adipocytes; in addition, the expression of oligopeptide transporter genes has been confirmed in pre-adipocytes. Thus, it is tempting to speculate that the target cells of Pro-Hyp are precursor cells. Pro-Hyp is generated endogenously when collagen turnover is enhanced, such as in an ear inflamed by contact dermatitis, and ingested Pro-Hyp appears in the same dermatitic ear when ingested orally. Thus, endogenous and food-derived Pro-Hyp co-localizes in the same tissue and may co-interact. Further studies on Pro- Hyp may reveal novel interactions between homeostasis of the tissue and this animal-derived nutrient.