In using a reversed hypoosmotic lysis and resealing process, internalization of Naloxone or Naltrexone prodrugs as new opioid antagonists into red blood cells (RBC) can be obtained. We describe the entrapment method and haematological parameters of such RBC carriers. Percentages of internalization range between 35% and 70%, depending on the prodrug. The stability of the different prodrugs within RBC, after in vitro internalization have been compared at 4 degrees C and 37 degrees C. These studies were performed in order to screen and choose the most interesting prodrugs for in vivo studies. Some prodrugs tested appeared to be stable after 24 hours of incubation, but others were not. The intracellular ATP and 2,3 BPG concentrations of RBC carriers were similar to the control.