In this study we tested the effect of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and a combination of these immunotherapeutics on clonogenic growth of cell lines and primary cultures of malignant human brain tumors. Out of 29 primary cultures studied, 5 were inhibited 50% or more by IFN-gamma (10 ng/ml), 6 were inhibited 50% or more by TNF-alpha (10 ng/ml) and 14 were inhibited 50% or more by a combination of IFN-gamma (10 ng/ml) and TNF-alpha (10 ng/ml). The doses of the immunotherapeutics used in this in vitro study are achievable in serum after intravenous administration of IFN-gamma and TNF-alpha without causing unacceptable side effects. We believe that some glioma patients and some patients with brain metastases will benefit from receiving treatment with IFN-gamma, TNF-alpha or a combination of these immunotherapeutics. The patients should be selected for treatment with these immunotherapeutics according to in vitro sensitivity results.