Intravenous injection of fluorescein isothiocyanate-modified syngeneic spleen cells (FITC-SSC) into mice induced T cell-independent, anti-hapten plaque-forming cell responses. In contrast to the high immunogenicity of FITC-coupled SSC or bone marrow cells, thymus, lymph node or peritoneal exudate cells were poorly immunogenic. Further analysis showed that FITC-syngeneic peripheral blood red cells were as immunogenic as FITC-SSC containing a similar number of red cells. The immunogenicity of the red cells was confirmed by treatment of FITC-SSC with 0.83% ammonium chloride before sensitization with FITC. This procedure almost totally abolished the immunogenicity regardless of the concentration of hapten with which they were sensitized. In addition, heat treatment or fixation with glutaraldehyde destroyed the immunogenicity of FITC-SSC.