Immunotherapy of mice with preexisting cancers with heat shock protein preparations derived from autologous cancer resulted in retarded progression of the primary cancer, a reduced metastatic load, and prolongation of life-span. Treatment with heat shock protein preparations derived from cancers other than the autologous cancer did not provide significant protection. Spontaneous cancers (lung cancer and melanoma), chemically induced cancers (fibrosarcoma and colon carcinoma), and an ultraviolet radiation-induced spindle cell carcinoma were tested, and the results support the efficacy of autologous cancer–derived heat shock protein–peptide complexes in immunotherapy of cancers without the need to identify specific tumor antigenic epitopes.