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Short-term efficacy of local gamma interferon delivered via a single injection of an adenovirus-gamma interferon vector has been reported in immunocompetent animals which develop spontaneous liver cancer. However the long-term outcome was not examined. The aim of this randomized trial was to assess in an immunodeficient mouse ectopic model the benefit, if any, of the long-term efficacy of intratumoral injections of gamma interferon itself.77 mice were randomly assigned to 4 groups. Gamma interferon treated groups received a dose of 5000, 10000 or 20000 IU per animal versus phosphate-buffered saline. The follow-up lasted 46 days.Significant differences were noted in mice receiving 20000 IU compared to controls: increase in survival (p=0.0485), slowing down of tumor growth in large tumors (p=0.009), increase in necrosis (p=0.004). The preferential staining in necrotic areas with anti-Class II antibody and the accumulation of nuclear debris indicated that neutrophils were involved.Gamma interferon could accentuate the migration of non-specific immune cells to necrotic areas which occur spontaneously in large tumors. These results in animals bearing large tumor suggest that it may be worthwhile to explore local gamma interferon delivery to patients with extensive hepatocarcinoma.