Current treatments for malignant gliomas are still largely ineffective in significantly improving prognosis. We have investigated the efficacy of treating established rat C6 glioma by in situ retroviral delivery of IFN-gamma cDNA. Ecotropic retrovirus packaging cells were transfected with a retroviral vector containing the mouse IFN-gamma gene. The IFN-gamma packaging cells were stereotactically implanted into established intracranial C6 glioma in immunocompetent Wistar rats, resulting in the eradication of these tumors. All IFN-gamma-treated rats survived to 92 days after C6 implantation (an arbitrary end point) compared with 14 days for controls. Analysis of these treated brains showed that the established C6 tumors had been completely eradicated by this time-point with brain morphology appearing normal. The IFN-gamma-mediated tumoricidal activity resulted from an apparent interplay of B and T cell components of the immune system, as well as the inhibition of tumor angiogenesis. This therapeutic strategy may provide an effective method of eradicating established intracranial tumors.