To evaluate the role of blood cells in inter-organ amino acid transport, and in the estimates of regional protein turnover, we studied the effects of plasma vs. whole-blood sampling on regional leucine kinetics in postabsorptive humans. Studies were carried out by combining the arterio-venous difference technique with the measurement of ¹⁴C- and ¹⁵N-leucine isotope exchange across the human kidney, the splanchnic area, and the leg. In the kidney, whole-blood derived rates of leucine-carbon appearance (Ra), disposal (Rd), and net balance were greater (by 3-15 times)(p<0.035) than those calculated in plasma. In addition, the netleucine-carbon (i.e. protein) balance across the kidney was negative in whole-blood (-5.6±1.3 µmol/min x 1.73 m², p<0.01 vs. zero), but neutral in plasma (-0.24±1.33, p = NS from zero; p<0.01 vs. whole-blood). A net leucine transport out of renal cells was shown in blood but not in plasma. In contrast, leucine-carbon Ra, Rd, net balance, and net transport, in both the splanchnic area the leg, were similar in whole-blood and plasma. These data suggest that blood cells play a key role in leucine transport out of the kidney, and consequently, in the leucine-derived estimates of renal protein degradation and net balance, at variance with what observed across the splanchnic organs or the leg. These data also emphasize the need for complete whole-blood arterio-venous measurements in order to accurately estimate protein turnover across the kidney.