To evaluate the contribution of blood cellular elements to inter-organ transport of amino acids, net exchange across the leg and splanchnic bed of 17 amino acids was determined in seven healthy postabsorptive subjects by use of both whole blood and plasma for analysis. Arterial-portal venous differences were measured in five additional subjects undergoing elective cholecystectomy. By use of whole blood, significant net release of amino acids was noted from the leg and gut, while a consistent uptake was observed by the splanchnic bed. The output of alanine from the leg and gut and the uptake of this amino acid by the splanchnic bed exceeded that of all other amino acids and accounted for 35-40% of total amino-acid exchange. Transport by way of plasma could not account for total tissue release or uptake of alanine, threonine, serine, glutamine, methionine, leucine, isoleucine, tyrosine, and citrulline. For each of these amino acids, significant tissue exchange was calculated to occur by way of the blood cellular elements, the direction of which generally paralleled the net shifts occurring in plasma. For alanine, 30% of its output from the leg and gut and 22% of its uptake by the splanchnic area occurred by way of blood cells. We conclude that the blood cellular elements, presumably erythrocytes, contribute substantially to the net flux of amino acids from muscle and gut to liver in normal postabsorptive humans. Alanine predominates in the inter-organ transfer of amino acids occurring by way of blood cells as well as plasma.