Intradermal vaccinations with Bacillus Calmette-Guérin (BCG) and viable but nontumorigenic syngeneic hepatocarcinoma cell vaccines were used successfully to treat micrometastatic disease experimentally induced in inbred guinea pigs at 100 times the minimal lethal dose. Several complications have been associated with the use of viable BCG organisms in the treatment of cancer patients and, in this animal model, intradermal administration of BCG uniformly results in severe ulceration and eschar formation at the injection sites leading to secondary microbial invasion and regional lymphadenopathy. We now report the use of isoniazid (Nydrazid) as part of an active specific immunization regimen. Incorporation of isoniazid into the immunization procedure for two weeks alleviates or reduces the side effects of BCG infection. Moreover, with proper consideration of BCG dosage, isoniazid does not impair the efficacy of the BCG plus tumor cell vaccines.