The cytokine signaling pathways that activate the Janus family of tyrosine kinases (Jaks) and the "signal transducers and activators of transcription" (Stats) have been well characterized in mammalian systems. Work shown here provides evidence that an analogous signaling pathway exists in Drosophila melanogaster. Because many of the ligand-receptor pairs in Drosophila have not been fully characterized, it was necessary to bypass the receptor stimulation event that normally triggers intracellular Jak/Stat activation. This was done by treating Drosophila Schneider 2 cells with vanadate/peroxide, which has been shown to closely mimic some signaling events triggered by interferon gamma, including the activation of Jak1, Jak2, and the Stat1 alpha protein. Evidence presented here demonstrates that vanadate/peroxide can induce a gamma response region binding complex in Drosophila Schneider 2 cells. This complex contains two phosphoproteins of 100 and 150 kDa, respectively, and shares many features with the vanadate/peroxide-stimulated binding complex in the mammalian system. Southern blot analysis of genomic DNA using the src homology domain 2 (SH2) of Stat1 alpha confirms the presence of a related gene in the Drosophila genome.