The effect of inoculating formalinized syngeneic or allogeneic Rous sarcoma cells on the growth of Rous sarcoma virus (RSV)-induced tumors in two related inbred strains of chickens was studied. Chickens from both strains that received three weakly inoculations of syngeneic tumor cells had a significant increase in tumor growth and mortality after subsequent challenge with RSV. Development of RSV-induced tumors in chickens pretreated with formalinized allogeneic tumor cells (i.e. incompatible for major histocompatibility complex (MHC) antigens) was similar to what we observed in nonpretreated control chickens. The finding that the tumor-host relationship is altered only in chickens pretreated with formalinized syngeneic RSV-transformed cells, suggests that tumor-associated antigens of Rous sarcomas are modified MHC antigens analogous to "altered self" antigens thought to be present on certain virus-infected cells. If this hypothesis is correct, the results we obtained with formalin-killed syngeneic tumor cells can be explained on the basis of three possible mechanisms: immunological enhancement, immune tolerance or induction of antibody to anti-tumor idiotype. The merits of each mechanism in accounting for the results are discussed.