Phenylalanine or tryptophan entrapped in small unilamellar liposomes was used to transport Phe or Trp across the red blood cell membrane. The incorporation of Phe or Trp into RBCs via liposomes markedly inhibited and reversed the in vitro sickling of deoxy Hb S. Furthermore, normal and SS RBCs loaded with Phe or Trp did not exhibit significant change in osmotic fragility, mechanical fragility, autohemolysis, and glycolysis when compared to untreated RBCs. In addition, the oxygen affinity measured as the P50 and concentrations of 2,3-DPG and ATP were not affected by the incorporation of Phe or Trp into AA or SS RBCs. These results demonstrate that this liposomal transport system which transferred Phe and Trp into intact RBCs did not have any adverse effect on RBC metabolism and function, and may have therapeutic implications in the treatment of sickle cell disease.