OBJECTIVE: This report describes four patients with malignant brain tumors in whom regression or cure seems to be related to infection with bacteria. METHODS: An analysis of the four clinical cases reported and a review of the literature produced a comprehensive body of both experimental and clinical data concerning the antineoplastic properties of bacteria. RESULTS: Although direct oncolytic effects from bacteria have been suggested, immune adjuvant responses to tumor suppression are emphasized. In one of our patients, infiltration of numerous granulocytes and lymphocytes into the tumor at the time of initial surgery was observed, suggesting that a spontaneous immune reaction had begun. Also, in two other patients, tumor aggression occurred in association with a bacterial process that was not in direct contact with the tumor. In three of the cases described, Enterobacter aerogenes was recovered from the microbial cultures. Whether the presence of this organism was coincidental or whether this organism plays an important role in tumor defense is not known; however, a specific cross-reactive immunological attack to the tumor is suggested. CONCLUSION: The case histories presented in conjunction with the relevant literature reviewed support the concept that microbial infections may influence immune responses in brain tumor defense.