The metabolic pathways of denatured collagen (gelatin) and hyaluronan were studied by injecting labelled macromolecules into the mesentery of rats. The label, [125I]tyraminecellobiose is trapped intracellularly after endocytosis, allowing localization of the site of uptake. Mesenteric and thoracic lymph was sampled for 6 h in anaesthetized rats. Separate rats were investigated after an awake period of 6 or 24 h. About 30% of the gelatin remained at the site of injection and of the remaining activity 1.7% was recovered in lymph, 11 yo in the liver and 15% in the kidneys, whereas 3 h after an intravenous injection of gelatin>70% was recovered in the liver. The change in preferable site of uptake from the liver to the kidney was attributed to local degradation in the mesentery as confirmed by chromatography of tissue extracts and lymph.Following hyaluronan injection and 6 h lymph sampling approximately 30% was left at the site of injection and of the remaining activity 5.7% was recovered in lymph. After an awake period of 6 or 24 h, 30% was regained in the liver. The recoveries in other organs were negligible and mesenteric lymph nodes seem quantitatively unimportant in the uptake of hyaluronan or gelatin from lymph or blood.The liver has a central role in intestinal hyaluronan metabolism, while denatured collagen is more prone to local degradation with remote uptake shared between the liver and the kidney.