The complex processes that determine the outcome of the interaction of tumor and host were explored in the operationally simple and reproducible rat D-12 ascites tumor model. Animals exhibit weak spontaneous resistance against this tumor that is not augmented by repeated inoculation, by various routes, of irradiated syngeneic D-12 tumor cells, but considerably enhanced after local administration of heat-killed Corynebacterium parvum (CP) or Listeria monocytogenes (LM) organisms. Inoculation of conventional or monoclonal anti-rat IFN gamma antibodies into the same compartment did not affect spontaneous tumor resistance, but largely abrogated the tumor-protective effect triggered by CP or LM. Our findings support the concept that IFN gamma, produced by T cells in the course of the specific immune response raised against immunogenic micro-organisms, is able to enhance and to maintain local tumor resistance and thus to strengthen the capacity of the host to cope with a non-immunogenic tumor.