Both plasma and red blood cells contain amino acids (AA), but the relative amount of AA transferred from each vascular compartment to the tissues remains unclear. For splanchnic tissues, the relative transfers between the plasma, the red blood cells and the tissues may vary with nutritional state, but whether the same situation pertains for other tissues is not known. The current study focused on the transfer of lysine from plasma and red blood cells across the hindquarters of sheep offered four levels of intakes (0.5, 1.0, 1.5 and 2.5 x maintenance energy). This design, coupled with use of [U-13C]lysine as tracer, also allowed the effect of intake on protein kinetics to be examined. At all intakes, the concentration of lysine in the sheep' red blood cells exceeded that in plasma by 50% (P<0.001), while the distribution of labelled lysine between the plasma and the red blood cells was 0.71:0.29. Net lysine uptake by the hindquarters increased in a linear manner (P<0.001) with intake, with more than 90% extracted from the plasma. Free lysine enrichments in plasma from the posterior vena cava were less than that from the artery (P<0.001), but those in red blood cells were not different between the artery and vein. The red blood cells thus play a minor role in the transfers to and from the hindquarter tissues, regardless of intake. Based on plasma transfers and the enrichment of lysine in arterial plasma, hindquarter protein synthesis increased linearly with intake (P<0.001). In contrast, protein breakdown was unaffected by intake. The contribution of hindquarter protein synthesis to whole-body lysine flux remained unchanged with intake (18-20%).