Membrane recombinant CD4 was electroinserted into the plasma membrane of red blood cells (RBCs) from four HIV patients. CD4 had been labeled with 125I before electroinsertion. The RBCs-CD4-125I were labeled with 51Cr and autotransfused to the donor patients. The hematological indexes and the P50 value of the RBCs were not modified by the electroinsertion of CD4. The life span of the RBCs was not affected by electroinsertion of CD4 (t1/2 approximately 30 days), whereas the exposed CD4 showed a kinetics of disappearance characterized by two half-life times: a short one (t1/2 approximately 1 day) and a long one approximately equal to that of the RBCs. No side effects or anti-CD4 immune responses were observed in patients over a period of 28 days. The RBC-CD4 entity appears to be long-lived and has no adverse effect in HIV patients.