The exchange of docosahexaenoic acid (22:6n-3) within lipid pools in rat and human has been followed as a function of time after the ingestion of triglycerides (TG) containing 22:6n-3 labeled with C-13 (C-13 22:6n-3). The C-13 abundance in the fatty acid was measured by gas-chromatography-combustion isotope ratio mass spectrometry which allowed the detection of 0.001 atom C-13 percent C-12. Th, C-13 22:6n-3 appearance was rapid in the TC of very low density lipoprotein plus chylomicron fraction, in which the maximal labeling was observed at 3 and 2 h after ingestion in rat and human, respectively. Concomitant with the TC utilization of this fraction by lipoprotein lipase from tissues, unesterified C-13 22:6n-3 appeared in the plasma albumin. C-13 22:6n-3 bound to albumin was mostly present in unesterified form before 12 h post-ingestion while after that period, lysophosphatidylcholine (lysoPC) bound to albumin carried higher C-13 22:6n-3 concentrations. These lyse-PC were mostly from hepatic origin and might represent a potential source of 22:6n-3 redistribution to tissues. The C-13 22:6n-3 uptake into rat brain PC and phosphatidylethanolamine was still increasing when the concentration of plasma unesterified C-13 22:6n-3 had already dropped to a minimal plateau value and during the period of maximal plasma circulation of C-13 22:6n-3-lysoPC bound to albumin. In contrast, the uptake of C-13 22:6n-3 into blood platelet PC occurred during the phase of important circulation of C-13-22:6n-3 bound to albumin, suggesting the in vivo efficiency of the Lands pathway for this fatty acid. It is concluded that C-13 22:6n-3 esterified in TG is rapidly absorbed and redistributed within plasma lipoproteins and that its redistribution within the two lipid species bound to;albumin might influence its uptake by platelets and rat brain.