Abstract: In the present study we wanted to investigate if human interferon-gamma (hIFN-γ) is functional in insect cells and performed experiments to test the possibility of interferon antiviral activity. Interferon-like molecules have not yet been identified in insects. We investigated if molecule(s) with functional and structural similarities to hIFN-γ could be involved in antiviral defense of Manduca sexta larvae in protection studies using hIFN-γ. Fifth-instar larvae of tobacco hornworm were inoculated with Galleria mellonella Nuclear Polyhedrosis Virus (NPV) that was lethal to 88% of larvae. Inoculation of larvae with recombinant hIFN-γ prior to infection with NPV induced an increased resistance to NPV infection when compared with larvae which received hIFN-γ following NPV infection and to controls which received only NPV. The most significant survival rate (67%) was observed in larvae which received hIFN-γ 6 h before NPV infection. Data obtained by different salt fractionations of hemolymph using Cibacron Blue agarose chromatography indicated possible isolation of an interferon-like insect molecule. This indicated that cytokine molecule(s) with activity similar to that of hIFN-γ could be important in antiviral defense by this insect.