SUMMARYAn apparent histoincompatibility was demonstrable between mice chronically infected with lymphocytic choriomeningitis (LCM) virus and their uninfected syngeneic counterparts. Transplants of whole skin from infected donors to uninfected recipients were consistently rejected within 12-14 days. Also rejected were transplants of single cell suspensions of a histocompatible adenocarcinoma when they were transferred from infected donors to uninfected recipients. Using infected cells or debris from infected cells as challenge antigens, a delayed-type of hypersensitivity reaction could be evoked in animals that had previously rejected infected tumor transplants or which were otherwise immunized with the virus. Lymph node cells harvested from mice previously injected with LCM virus were shown to have a destructive action upon mouse L cells which were chronically or acutely infected with the virus. It is suggested that cells chronically or acutely infected with LCM virus exhibit new antigenic determinants on the surface of the cytoplasmic membrane. An immune response directed against these new antigens might inflict irreparable damage upon such infected cells.