SUMMARY Treatment of lymphocytes with mitomycin C at 50 μg/ml inactivates their capacity to stimulate allogeneic lymphocytes in vitro, but does not alter their antigenic integrity, as measured by their ability to absorb specific antibody or stimulate specifically sensitized cells in vitro. Treatment of lymphocytes with mitomycin C at 10 or 25 μg/ml does not inactivate their capacity to stimulate allogeneic lymphocytes in vitro. The in vivo immunogenicity of normal or mitomycin C-treated cells was estimated by monitoring the response in the popliteal lymph node of recipient sheep. Treatment of allogeneic lymphocytes with mitomycin C (50 μg/ml caused a marked reduction in their in vivo immunogenicity. Cells incubated with this drug at 10 or 25 μg/ml were more immunogenic than cells treated with mitomycin C at 50 μg/ml, but were less immunogenic than normal cells. The treatment of xenogenic (rat) lymphocytes with mitomycin C at 50 μg/ml had no effect on the cellular or humoral response they generated in the sheep lymph node. These data indicate that allogeneic stimulation modulates the immunogenicity of allogeneic transplantation antigen.