The ability of bacillus Calmette-Guérin (BCG) to ausment the immunogenicity of a poorly immunogcnic, syngeneic ascites hepatoma (line 10 ) of strain-2 guinea pigs was studied in a model system characterized by simultaneous contralateral injection of immunizing (vaccine) and challenge (living tumor cell) preparations. Several immunization procedures were compared to determine conditions optimal for vaccine safety and therapeutic potency. Under the best conditions, palpable malignant tumors at the challenge site (up to 15-mm diameter) ceased growth and regressed completely due to a systemic tumor-specific immune response. Effective vaccines contained living BCG and viable line-10 cells. Vaccines with irradiated (12,000 R) tumor cells were as effective as those with unirradiated cells. Vaccines containing unirradiated tumor cells were occasionally tumor-igenic in animals with tumor at a distant site. Use of repeated vaccine injections or a larger dose of tumor cells in the vaccine did not improve the therapeutic effect. Vaccines not affecting growth of the challenge tumor were line-10 cells emulsified in complete Freund's adjuvant, irradiated line-10 cells without BCG, or line-1 cells (antigenically distinct tumor) mixed with BCG.