The present study was undertaken to identify the different amino acid transport pathways present in the human small intestine during the early gestational period. The uptake time courses of neutral (L-leucine, L-alanine, L-methionine), acidic (L-glutamic and D-aspartic acids), basic (L-lysine), and imino (L-proline) acids have been studied in brush border membrane vesicles isolated from both proximal and distal parts of the human fetal small intestine. Both Na(+)-dependent and Na(+)-independent uptake pathways have been identified all along the small intestine. The Na(+)-dependent systems are as follows: (a) the NBB system for neutral amino acids such as L-leucine and L-alanine; (b) the PHE system for L-methionine; (c) the x-ag system for L-glutamic and D-aspartic acids; and (d) the IMINO system for L-proline. The Na(+)-independent pathways are represented by the L system for most of the neutral amino acids and maybe L-proline and by the basic amino system y+ for L-lysine uptake. These results demonstrate that the different uptake pathways for transport of amino acids are present in the human fetal intestine and that their characteristics in terms of Na+ requirement and proximodistal activity gradient are already established in the early stages of the human development.