Tumor-derived purified heat shock protein (HSP), gp96, has tumor protective effect in a number of experimental cancers that include fibrosarcoma, hepatoma, and spindle cell carcinoma. The rationale for using gp96 as a vaccinating agent stems from the discovery that HSPs, including gp96, chaperone antigenic peptides for eventual recognition and elicitation of an immune response. The immune response generated by the HSP-peptide complex is specific to the tumor from which they are derived. The long-term objective of our studies is to develop a vaccine for primary and metastatic prostate cancer using tumor-derived HSPs. In the present study, we report our results on the tumor protective effect of irradiated Dunning G cells, or purified preparations of g96-peptide complexes as a tumor vaccine. Tumor incidence, latency, and tumor growth were the end points of measurement. Tumor bearing Copenhagen rats, made free of disease by surgical resection of the tumors resisted a fresh challenge of live Dunning G tumor cells. Vaccination with irradiated whole cells failed to elicit any resistance to tumor growth. Vaccination with Dunning G derived purified gp96-peptide complexes delayed both incidence and growth of Dunning G induced tumors. Inhibition of tumor growth was observed when gp96 was administered after tumor induction. Our data suggests that tumor derived gp96-peptide complexes can be used as an effective prophylactic and therapeutic agent even in poorly immunogenic cancer such as prostate cancer. Further investigations will determine specificity of action and define the immunological determinants and experimental conditions for its optimal activity.